Stem-loop-induced ribosome queuing in the uORF2/ATF4 overlap fine-tunes stress-induced human ATF4 translational control

Summary: Activating transcription factor 4 (ATF4) is a master transcriptional regulator of the integrated stress response, leading cells toward adaptation or death. ATF4’s induction under stress was thought to be due to delayed translation reinitiation, where the reinitiation-permissive upstream ope...
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Autor*in:	Anna M. Smirnova [verfasserIn] Vladislava Hronová [verfasserIn] Mahabub Pasha Mohammad [verfasserIn] Anna Herrmannová [verfasserIn] Stanislava Gunišová [verfasserIn] Denisa Petráčková [verfasserIn] Petr Halada [verfasserIn] Štěpán Coufal [verfasserIn] Michał Świrski [verfasserIn] Justin Rendleman [verfasserIn] Kristína Jendruchová [verfasserIn] Maria Hatzoglou [verfasserIn] Petra Beznosková [verfasserIn] Christine Vogel [verfasserIn] Leoš Shivaya Valášek [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2024

Schlagwörter:	CP: Molecular biology

Übergeordnetes Werk:	In: Cell Reports - Elsevier, 2015, 43(2024), 4, Seite 113976-
Übergeordnetes Werk:	volume:43 ; year:2024 ; number:4 ; pages:113976-

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1016/j.celrep.2024.113976

Katalog-ID:	DOAJ099748541

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245	1	0	\|a Stem-loop-induced ribosome queuing in the uORF2/ATF4 overlap fine-tunes stress-induced human ATF4 translational control
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520			\|a Summary: Activating transcription factor 4 (ATF4) is a master transcriptional regulator of the integrated stress response, leading cells toward adaptation or death. ATF4’s induction under stress was thought to be due to delayed translation reinitiation, where the reinitiation-permissive upstream open reading frame 1 (uORF1) plays a key role. Accumulating evidence challenging this mechanism as the sole source of ATF4 translation control prompted us to investigate additional regulatory routes. We identified a highly conserved stem-loop in the uORF2/ATF4 overlap, immediately preceded by a near-cognate CUG, which introduces another layer of regulation in the form of ribosome queuing. These elements explain how the inhibitory uORF2 can be translated under stress, confirming prior observations but contradicting the original regulatory model. We also identified two highly conserved, potentially modified adenines performing antagonistic roles. Finally, we demonstrated that the canonical ATF4 translation start site is substantially leaky scanned. Thus, ATF4’s translational control is more complex than originally described, underpinning its key role in diverse biological processes.
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700	0		\|a Anna Herrmannová \|e verfasserin \|4 aut
700	0		\|a Stanislava Gunišová \|e verfasserin \|4 aut
700	0		\|a Denisa Petráčková \|e verfasserin \|4 aut
700	0		\|a Petr Halada \|e verfasserin \|4 aut
700	0		\|a Štěpán Coufal \|e verfasserin \|4 aut
700	0		\|a Michał Świrski \|e verfasserin \|4 aut
700	0		\|a Justin Rendleman \|e verfasserin \|4 aut
700	0		\|a Kristína Jendruchová \|e verfasserin \|4 aut
700	0		\|a Maria Hatzoglou \|e verfasserin \|4 aut
700	0		\|a Petra Beznosková \|e verfasserin \|4 aut
700	0		\|a Christine Vogel \|e verfasserin \|4 aut
700	0		\|a Leoš Shivaya Valášek \|e verfasserin \|4 aut
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allfields	10.1016/j.celrep.2024.113976 doi (DE-627)DOAJ099748541 (DE-599)DOAJ0f04c695bf164ff7a96d9c1f5bcc5a53 DE-627 ger DE-627 rakwb eng QH301-705.5 Anna M. Smirnova verfasserin aut Stem-loop-induced ribosome queuing in the uORF2/ATF4 overlap fine-tunes stress-induced human ATF4 translational control 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Activating transcription factor 4 (ATF4) is a master transcriptional regulator of the integrated stress response, leading cells toward adaptation or death. ATF4’s induction under stress was thought to be due to delayed translation reinitiation, where the reinitiation-permissive upstream open reading frame 1 (uORF1) plays a key role. Accumulating evidence challenging this mechanism as the sole source of ATF4 translation control prompted us to investigate additional regulatory routes. We identified a highly conserved stem-loop in the uORF2/ATF4 overlap, immediately preceded by a near-cognate CUG, which introduces another layer of regulation in the form of ribosome queuing. These elements explain how the inhibitory uORF2 can be translated under stress, confirming prior observations but contradicting the original regulatory model. We also identified two highly conserved, potentially modified adenines performing antagonistic roles. Finally, we demonstrated that the canonical ATF4 translation start site is substantially leaky scanned. Thus, ATF4’s translational control is more complex than originally described, underpinning its key role in diverse biological processes. CP: Molecular biology Biology (General) Vladislava Hronová verfasserin aut Mahabub Pasha Mohammad verfasserin aut Anna Herrmannová verfasserin aut Stanislava Gunišová verfasserin aut Denisa Petráčková verfasserin aut Petr Halada verfasserin aut Štěpán Coufal verfasserin aut Michał Świrski verfasserin aut Justin Rendleman verfasserin aut Kristína Jendruchová verfasserin aut Maria Hatzoglou verfasserin aut Petra Beznosková verfasserin aut Christine Vogel verfasserin aut Leoš Shivaya Valášek verfasserin aut In Cell Reports Elsevier, 2015 43(2024), 4, Seite 113976- (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:43 year:2024 number:4 pages:113976- https://doi.org/10.1016/j.celrep.2024.113976 kostenfrei https://doaj.org/article/0f04c695bf164ff7a96d9c1f5bcc5a53 kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124724003048 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 43 2024 4 113976-
spelling	10.1016/j.celrep.2024.113976 doi (DE-627)DOAJ099748541 (DE-599)DOAJ0f04c695bf164ff7a96d9c1f5bcc5a53 DE-627 ger DE-627 rakwb eng QH301-705.5 Anna M. Smirnova verfasserin aut Stem-loop-induced ribosome queuing in the uORF2/ATF4 overlap fine-tunes stress-induced human ATF4 translational control 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Activating transcription factor 4 (ATF4) is a master transcriptional regulator of the integrated stress response, leading cells toward adaptation or death. ATF4’s induction under stress was thought to be due to delayed translation reinitiation, where the reinitiation-permissive upstream open reading frame 1 (uORF1) plays a key role. Accumulating evidence challenging this mechanism as the sole source of ATF4 translation control prompted us to investigate additional regulatory routes. We identified a highly conserved stem-loop in the uORF2/ATF4 overlap, immediately preceded by a near-cognate CUG, which introduces another layer of regulation in the form of ribosome queuing. These elements explain how the inhibitory uORF2 can be translated under stress, confirming prior observations but contradicting the original regulatory model. We also identified two highly conserved, potentially modified adenines performing antagonistic roles. Finally, we demonstrated that the canonical ATF4 translation start site is substantially leaky scanned. Thus, ATF4’s translational control is more complex than originally described, underpinning its key role in diverse biological processes. CP: Molecular biology Biology (General) Vladislava Hronová verfasserin aut Mahabub Pasha Mohammad verfasserin aut Anna Herrmannová verfasserin aut Stanislava Gunišová verfasserin aut Denisa Petráčková verfasserin aut Petr Halada verfasserin aut Štěpán Coufal verfasserin aut Michał Świrski verfasserin aut Justin Rendleman verfasserin aut Kristína Jendruchová verfasserin aut Maria Hatzoglou verfasserin aut Petra Beznosková verfasserin aut Christine Vogel verfasserin aut Leoš Shivaya Valášek verfasserin aut In Cell Reports Elsevier, 2015 43(2024), 4, Seite 113976- (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:43 year:2024 number:4 pages:113976- https://doi.org/10.1016/j.celrep.2024.113976 kostenfrei https://doaj.org/article/0f04c695bf164ff7a96d9c1f5bcc5a53 kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124724003048 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 43 2024 4 113976-
allfields_unstemmed	10.1016/j.celrep.2024.113976 doi (DE-627)DOAJ099748541 (DE-599)DOAJ0f04c695bf164ff7a96d9c1f5bcc5a53 DE-627 ger DE-627 rakwb eng QH301-705.5 Anna M. Smirnova verfasserin aut Stem-loop-induced ribosome queuing in the uORF2/ATF4 overlap fine-tunes stress-induced human ATF4 translational control 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Activating transcription factor 4 (ATF4) is a master transcriptional regulator of the integrated stress response, leading cells toward adaptation or death. ATF4’s induction under stress was thought to be due to delayed translation reinitiation, where the reinitiation-permissive upstream open reading frame 1 (uORF1) plays a key role. Accumulating evidence challenging this mechanism as the sole source of ATF4 translation control prompted us to investigate additional regulatory routes. We identified a highly conserved stem-loop in the uORF2/ATF4 overlap, immediately preceded by a near-cognate CUG, which introduces another layer of regulation in the form of ribosome queuing. These elements explain how the inhibitory uORF2 can be translated under stress, confirming prior observations but contradicting the original regulatory model. We also identified two highly conserved, potentially modified adenines performing antagonistic roles. Finally, we demonstrated that the canonical ATF4 translation start site is substantially leaky scanned. Thus, ATF4’s translational control is more complex than originally described, underpinning its key role in diverse biological processes. CP: Molecular biology Biology (General) Vladislava Hronová verfasserin aut Mahabub Pasha Mohammad verfasserin aut Anna Herrmannová verfasserin aut Stanislava Gunišová verfasserin aut Denisa Petráčková verfasserin aut Petr Halada verfasserin aut Štěpán Coufal verfasserin aut Michał Świrski verfasserin aut Justin Rendleman verfasserin aut Kristína Jendruchová verfasserin aut Maria Hatzoglou verfasserin aut Petra Beznosková verfasserin aut Christine Vogel verfasserin aut Leoš Shivaya Valášek verfasserin aut In Cell Reports Elsevier, 2015 43(2024), 4, Seite 113976- (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:43 year:2024 number:4 pages:113976- https://doi.org/10.1016/j.celrep.2024.113976 kostenfrei https://doaj.org/article/0f04c695bf164ff7a96d9c1f5bcc5a53 kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124724003048 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 43 2024 4 113976-
allfieldsGer	10.1016/j.celrep.2024.113976 doi (DE-627)DOAJ099748541 (DE-599)DOAJ0f04c695bf164ff7a96d9c1f5bcc5a53 DE-627 ger DE-627 rakwb eng QH301-705.5 Anna M. Smirnova verfasserin aut Stem-loop-induced ribosome queuing in the uORF2/ATF4 overlap fine-tunes stress-induced human ATF4 translational control 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Activating transcription factor 4 (ATF4) is a master transcriptional regulator of the integrated stress response, leading cells toward adaptation or death. ATF4’s induction under stress was thought to be due to delayed translation reinitiation, where the reinitiation-permissive upstream open reading frame 1 (uORF1) plays a key role. Accumulating evidence challenging this mechanism as the sole source of ATF4 translation control prompted us to investigate additional regulatory routes. We identified a highly conserved stem-loop in the uORF2/ATF4 overlap, immediately preceded by a near-cognate CUG, which introduces another layer of regulation in the form of ribosome queuing. These elements explain how the inhibitory uORF2 can be translated under stress, confirming prior observations but contradicting the original regulatory model. We also identified two highly conserved, potentially modified adenines performing antagonistic roles. Finally, we demonstrated that the canonical ATF4 translation start site is substantially leaky scanned. Thus, ATF4’s translational control is more complex than originally described, underpinning its key role in diverse biological processes. CP: Molecular biology Biology (General) Vladislava Hronová verfasserin aut Mahabub Pasha Mohammad verfasserin aut Anna Herrmannová verfasserin aut Stanislava Gunišová verfasserin aut Denisa Petráčková verfasserin aut Petr Halada verfasserin aut Štěpán Coufal verfasserin aut Michał Świrski verfasserin aut Justin Rendleman verfasserin aut Kristína Jendruchová verfasserin aut Maria Hatzoglou verfasserin aut Petra Beznosková verfasserin aut Christine Vogel verfasserin aut Leoš Shivaya Valášek verfasserin aut In Cell Reports Elsevier, 2015 43(2024), 4, Seite 113976- (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:43 year:2024 number:4 pages:113976- https://doi.org/10.1016/j.celrep.2024.113976 kostenfrei https://doaj.org/article/0f04c695bf164ff7a96d9c1f5bcc5a53 kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124724003048 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 43 2024 4 113976-
allfieldsSound	10.1016/j.celrep.2024.113976 doi (DE-627)DOAJ099748541 (DE-599)DOAJ0f04c695bf164ff7a96d9c1f5bcc5a53 DE-627 ger DE-627 rakwb eng QH301-705.5 Anna M. Smirnova verfasserin aut Stem-loop-induced ribosome queuing in the uORF2/ATF4 overlap fine-tunes stress-induced human ATF4 translational control 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Activating transcription factor 4 (ATF4) is a master transcriptional regulator of the integrated stress response, leading cells toward adaptation or death. ATF4’s induction under stress was thought to be due to delayed translation reinitiation, where the reinitiation-permissive upstream open reading frame 1 (uORF1) plays a key role. Accumulating evidence challenging this mechanism as the sole source of ATF4 translation control prompted us to investigate additional regulatory routes. We identified a highly conserved stem-loop in the uORF2/ATF4 overlap, immediately preceded by a near-cognate CUG, which introduces another layer of regulation in the form of ribosome queuing. These elements explain how the inhibitory uORF2 can be translated under stress, confirming prior observations but contradicting the original regulatory model. We also identified two highly conserved, potentially modified adenines performing antagonistic roles. Finally, we demonstrated that the canonical ATF4 translation start site is substantially leaky scanned. Thus, ATF4’s translational control is more complex than originally described, underpinning its key role in diverse biological processes. CP: Molecular biology Biology (General) Vladislava Hronová verfasserin aut Mahabub Pasha Mohammad verfasserin aut Anna Herrmannová verfasserin aut Stanislava Gunišová verfasserin aut Denisa Petráčková verfasserin aut Petr Halada verfasserin aut Štěpán Coufal verfasserin aut Michał Świrski verfasserin aut Justin Rendleman verfasserin aut Kristína Jendruchová verfasserin aut Maria Hatzoglou verfasserin aut Petra Beznosková verfasserin aut Christine Vogel verfasserin aut Leoš Shivaya Valášek verfasserin aut In Cell Reports Elsevier, 2015 43(2024), 4, Seite 113976- (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:43 year:2024 number:4 pages:113976- https://doi.org/10.1016/j.celrep.2024.113976 kostenfrei https://doaj.org/article/0f04c695bf164ff7a96d9c1f5bcc5a53 kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124724003048 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 43 2024 4 113976-
language	English
source	In Cell Reports 43(2024), 4, Seite 113976- volume:43 year:2024 number:4 pages:113976-
sourceStr	In Cell Reports 43(2024), 4, Seite 113976- volume:43 year:2024 number:4 pages:113976-
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	CP: Molecular biology Biology (General)
isfreeaccess_bool	true
container_title	Cell Reports
authorswithroles_txt_mv	Anna M. Smirnova @@aut@@ Vladislava Hronová @@aut@@ Mahabub Pasha Mohammad @@aut@@ Anna Herrmannová @@aut@@ Stanislava Gunišová @@aut@@ Denisa Petráčková @@aut@@ Petr Halada @@aut@@ Štěpán Coufal @@aut@@ Michał Świrski @@aut@@ Justin Rendleman @@aut@@ Kristína Jendruchová @@aut@@ Maria Hatzoglou @@aut@@ Petra Beznosková @@aut@@ Christine Vogel @@aut@@ Leoš Shivaya Valášek @@aut@@
publishDateDaySort_date	2024-01-01T00:00:00Z
hierarchy_top_id	684964562
id	DOAJ099748541
language_de	englisch
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Smirnova</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Stem-loop-induced ribosome queuing in the uORF2/ATF4 overlap fine-tunes stress-induced human ATF4 translational control</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2024</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Summary: Activating transcription factor 4 (ATF4) is a master transcriptional regulator of the integrated stress response, leading cells toward adaptation or death. 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callnumber-first	Q - Science
author	Anna M. Smirnova
spellingShingle	Anna M. Smirnova misc QH301-705.5 misc CP: Molecular biology misc Biology (General) Stem-loop-induced ribosome queuing in the uORF2/ATF4 overlap fine-tunes stress-induced human ATF4 translational control
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topic_title	QH301-705.5 Stem-loop-induced ribosome queuing in the uORF2/ATF4 overlap fine-tunes stress-induced human ATF4 translational control CP: Molecular biology
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title	Stem-loop-induced ribosome queuing in the uORF2/ATF4 overlap fine-tunes stress-induced human ATF4 translational control
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title_full	Stem-loop-induced ribosome queuing in the uORF2/ATF4 overlap fine-tunes stress-induced human ATF4 translational control
author_sort	Anna M. Smirnova
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author_browse	Anna M. Smirnova Vladislava Hronová Mahabub Pasha Mohammad Anna Herrmannová Stanislava Gunišová Denisa Petráčková Petr Halada Štěpán Coufal Michał Świrski Justin Rendleman Kristína Jendruchová Maria Hatzoglou Petra Beznosková Christine Vogel Leoš Shivaya Valášek
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title_sort	stem-loop-induced ribosome queuing in the uorf2/atf4 overlap fine-tunes stress-induced human atf4 translational control
callnumber	QH301-705.5
title_auth	Stem-loop-induced ribosome queuing in the uORF2/ATF4 overlap fine-tunes stress-induced human ATF4 translational control
abstract	Summary: Activating transcription factor 4 (ATF4) is a master transcriptional regulator of the integrated stress response, leading cells toward adaptation or death. ATF4’s induction under stress was thought to be due to delayed translation reinitiation, where the reinitiation-permissive upstream open reading frame 1 (uORF1) plays a key role. Accumulating evidence challenging this mechanism as the sole source of ATF4 translation control prompted us to investigate additional regulatory routes. We identified a highly conserved stem-loop in the uORF2/ATF4 overlap, immediately preceded by a near-cognate CUG, which introduces another layer of regulation in the form of ribosome queuing. These elements explain how the inhibitory uORF2 can be translated under stress, confirming prior observations but contradicting the original regulatory model. We also identified two highly conserved, potentially modified adenines performing antagonistic roles. Finally, we demonstrated that the canonical ATF4 translation start site is substantially leaky scanned. Thus, ATF4’s translational control is more complex than originally described, underpinning its key role in diverse biological processes.
abstractGer	Summary: Activating transcription factor 4 (ATF4) is a master transcriptional regulator of the integrated stress response, leading cells toward adaptation or death. ATF4’s induction under stress was thought to be due to delayed translation reinitiation, where the reinitiation-permissive upstream open reading frame 1 (uORF1) plays a key role. Accumulating evidence challenging this mechanism as the sole source of ATF4 translation control prompted us to investigate additional regulatory routes. We identified a highly conserved stem-loop in the uORF2/ATF4 overlap, immediately preceded by a near-cognate CUG, which introduces another layer of regulation in the form of ribosome queuing. These elements explain how the inhibitory uORF2 can be translated under stress, confirming prior observations but contradicting the original regulatory model. We also identified two highly conserved, potentially modified adenines performing antagonistic roles. Finally, we demonstrated that the canonical ATF4 translation start site is substantially leaky scanned. Thus, ATF4’s translational control is more complex than originally described, underpinning its key role in diverse biological processes.
abstract_unstemmed	Summary: Activating transcription factor 4 (ATF4) is a master transcriptional regulator of the integrated stress response, leading cells toward adaptation or death. ATF4’s induction under stress was thought to be due to delayed translation reinitiation, where the reinitiation-permissive upstream open reading frame 1 (uORF1) plays a key role. Accumulating evidence challenging this mechanism as the sole source of ATF4 translation control prompted us to investigate additional regulatory routes. We identified a highly conserved stem-loop in the uORF2/ATF4 overlap, immediately preceded by a near-cognate CUG, which introduces another layer of regulation in the form of ribosome queuing. These elements explain how the inhibitory uORF2 can be translated under stress, confirming prior observations but contradicting the original regulatory model. We also identified two highly conserved, potentially modified adenines performing antagonistic roles. Finally, we demonstrated that the canonical ATF4 translation start site is substantially leaky scanned. Thus, ATF4’s translational control is more complex than originally described, underpinning its key role in diverse biological processes.
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container_issue	4
title_short	Stem-loop-induced ribosome queuing in the uORF2/ATF4 overlap fine-tunes stress-induced human ATF4 translational control
url	https://doi.org/10.1016/j.celrep.2024.113976 https://doaj.org/article/0f04c695bf164ff7a96d9c1f5bcc5a53 http://www.sciencedirect.com/science/article/pii/S2211124724003048 https://doaj.org/toc/2211-1247
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author2	Vladislava Hronová Mahabub Pasha Mohammad Anna Herrmannová Stanislava Gunišová Denisa Petráčková Petr Halada Štěpán Coufal Michał Świrski Justin Rendleman Kristína Jendruchová Maria Hatzoglou Petra Beznosková Christine Vogel Leoš Shivaya Valášek
author2Str	Vladislava Hronová Mahabub Pasha Mohammad Anna Herrmannová Stanislava Gunišová Denisa Petráčková Petr Halada Štěpán Coufal Michał Świrski Justin Rendleman Kristína Jendruchová Maria Hatzoglou Petra Beznosková Christine Vogel Leoš Shivaya Valášek
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doi_str	10.1016/j.celrep.2024.113976
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up_date	2024-07-04T00:10:54.738Z
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Smirnova</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Stem-loop-induced ribosome queuing in the uORF2/ATF4 overlap fine-tunes stress-induced human ATF4 translational control</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2024</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Summary: Activating transcription factor 4 (ATF4) is a master transcriptional regulator of the integrated stress response, leading cells toward adaptation or death. ATF4’s induction under stress was thought to be due to delayed translation reinitiation, where the reinitiation-permissive upstream open reading frame 1 (uORF1) plays a key role. Accumulating evidence challenging this mechanism as the sole source of ATF4 translation control prompted us to investigate additional regulatory routes. We identified a highly conserved stem-loop in the uORF2/ATF4 overlap, immediately preceded by a near-cognate CUG, which introduces another layer of regulation in the form of ribosome queuing. These elements explain how the inhibitory uORF2 can be translated under stress, confirming prior observations but contradicting the original regulatory model. We also identified two highly conserved, potentially modified adenines performing antagonistic roles. Finally, we demonstrated that the canonical ATF4 translation start site is substantially leaky scanned. Thus, ATF4’s translational control is more complex than originally described, underpinning its key role in diverse biological processes.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">CP: Molecular biology</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Biology (General)</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Vladislava Hronová</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Mahabub Pasha Mohammad</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Anna Herrmannová</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Stanislava Gunišová</subfield><subfield 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Jendruchová</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Maria Hatzoglou</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Petra Beznosková</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Christine Vogel</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Leoš Shivaya Valášek</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Cell Reports</subfield><subfield code="d">Elsevier, 2015</subfield><subfield code="g">43(2024), 4, Seite 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Stem-loop-induced ribosome queuing in the uORF2/ATF4 overlap fine-tunes stress-induced human ATF4 translational control

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