So close, no matter how far: multiple paths connecting transcription to mRNA translation in eukaryotes

Slobodin, Boris; Dikstein, Rivka

doi:10.15252/embr.202050799

Cited by 23 publications

(16 citation statements)

References 291 publications

(398 reference statements)

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“…Because the increased levels of the XBP1u mRNA in eIF2α-P-deficient cells was the result of transcriptional activation and not increased mRNA stability, we also conclude that stabilization of the XBP1 mRNA during the acute UPR Mohammed et al (2022) phase is not coupled to transcriptional induction of the XBP1 gene (Fig. 1F), as has been previously suggested (Slobodin et al 2020).…”

Section: Acute Upr-induced Translation Inhibition Stabilizes Xbp1u Mrnasupporting

confidence: 81%

“…Mechanisms linking transcription to mRNA translation, stability, and poly(A) tail length have recently been reported (Slobodin et al 2020;Slobodin et al 2017;Slobodin and Dikstein 2020). It was shown that reduced transcription dynamics correlated with enhanced m 6 A base modification, increased deadenylation activity, shorter poly(A) tails, and decreased mRNA stability of the target mRNAs (Slobodin et al 2020). On the other hand, enhanced transcription correlated with less m 6 A deposition on mRNAs and positive regulation of translational efficiency (Slobodin et al 2017).…”

Section: Discussionmentioning

confidence: 99%

“…The accumulation of long poly(A) tail XBP1 mRNA parallels its increased synthesis during ER stress. Mechanisms linking transcription to mRNA translation, stability, and poly(A) tail length have recently been reported (Slobodin et al 2020; Slobodin et al 2017; Slobodin and Dikstein 2020). It was shown that reduced transcription dynamics correlated with enhanced m 6 A base modification, increased deadenylation activity, shorter poly(A) tails, and decreased mRNA stability of the target mRNAs (Slobodin et al 2020).…”

Section: Discussionmentioning

confidence: 99%

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Newly synthesized mRNA escapes translational repression during the acute phase of the mammalian unfolded protein response

Alzahrani

Guan

Zagore

et al. 2022

Preprint

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Endoplasmic Reticulum (ER) stress, caused by the accumulation of misfolded proteins in the ER, elicits a homeostatic mechanism known as the Unfolded Protein Response (UPR). The UPR reprograms gene expression to promote adaptation to chronic ER stress. The UPR comprises an acute phase involving inhibition of bulk protein synthesis and a chronic phase of transcriptional induction coupled with the partial recovery of protein synthesis. However, the role of transcriptional regulation in the acute phase of the UPR is not well understood. Here we analyzed the fate of newly synthesized mRNA encoding the protective and homeostatic transcription factor X-box binding protein 1 (XBP1) during this acute phase. We have previously shown that global translational repression induced by the acute UPR was characterized by decreased translation and increased stability of XBP1 mRNA. We demonstrate here that this stabilization is independent of new transcription. In contrast, we show XBP1 mRNA newly synthesized during the acute phase accumulates with long poly(A) tails and escapes translational repression. Inhibition of nascent RNA polyadenylation during the acute phase decreased cell survival with no effect in unstressed cells. Furthermore, during the chronic phase of the UPR, levels of XBP1 mRNA with long poly(A) tails decreased in a manner consistent with co-translational deadenylation. Finally, additional pro-survival, transcriptionally-induced mRNAs show similar regulation, supporting the broad significance of the pre-steady state UPR in translational control during ER stress. We conclude that the biphasic regulation of poly(A) tail length during the UPR represents a previously unrecognized pro-survival mechanism of mammalian gene regulation.

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Section: Acute Upr-induced Translation Inhibition Stabilizes Xbp1u Mrnasupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Newly synthesized mRNA escapes translational repression during the acute phase of the mammalian unfolded protein response

Alzahrani

Guan

Zagore

et al. 2022

Preprint

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“…The relationship between transcription and translation in eukaryotes remains poorly understood [428]; however, a deep interconnection between these stages of protein expression is expected. An integrative response to stress at all levels of the gene expression process was recently described for Arabidopsis [429].…”

Section: Discussionmentioning

confidence: 99%

Localization and Functional Roles of Components of the Translation Apparatus in the Eukaryotic Cell Nucleus

Kachaev

Ivashchenko

Kozlov

et al. 2021

Cells

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Components of the translation apparatus, including ribosomal proteins, have been found in cell nuclei in various organisms. Components of the translation apparatus are involved in various nuclear processes, particularly those associated with genome integrity control and the nuclear stages of gene expression, such as transcription, mRNA processing, and mRNA export. Components of the translation apparatus control intranuclear trafficking; the nuclear import and export of RNA and proteins; and regulate the activity, stability, and functional recruitment of nuclear proteins. The nuclear translocation of these components is often involved in the cell response to stimulation and stress, in addition to playing critical roles in oncogenesis and viral infection. Many components of the translation apparatus are moonlighting proteins, involved in integral cell stress response and coupling of gene expression subprocesses. Thus, this phenomenon represents a significant interest for both basic and applied molecular biology. Here, we provide an overview of the current data regarding the molecular functions of translation factors and ribosomal proteins in the cell nucleus.

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“…Depending on the type, IRESs require no or only a few translation factors 23 . IRESs are also present in 5ʹ-UTRs of select cellular transcripts 24 , 25 . Unlike viral IRESs, cellular IRESs may exhibit weak secondary structures 26 , suggesting that RNA structure is not the sole determinant of the IRES activity.…”

Section: Introductionmentioning

confidence: 99%

A translation enhancer element from black beetle virus engages yeast eIF4G1 to drive cap-independent translation initiation

Trainor

Ghosh

Pestov

et al. 2021

Sci Rep

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Cap-independent translation initiation plays crucial roles in fine-tuning gene expression under global translation shutdown conditions. Translation of uncapped or de-capped transcripts can be stimulated by Cap-independent translation enhancer (CITE) elements, but the mechanisms of CITE-mediated translation initiation remain understudied. Here, we characterized a short 5ʹ-UTR RNA sequence from black beetle virus, BBV-seq. Mutational analysis indicates that the entire BBV-seq is required for efficient translation initiation, but this sequence does not operate as an IRES-type module. In yeast cell-free translation extracts, BBV-seq promoted efficient initiation on cap-free mRNA using a scanning mechanism. Moreover, BBV-seq can increase translation efficiency resulting from conventional cap-dependent translation initiation. Using genetic approaches, we found that BBV-seq exploits RNA-binding properties of eIF4G1 to promote initiation. Thus, BBV-seq constitutes a previously uncharacterized short, linear CITE that influences eIF4G1 to initiate 5′ end-dependent, cap-independent translation. These findings bring new insights into CITE-mediated translational control of gene expression.

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So close, no matter how far: multiple paths connecting transcription to mRNA translation in eukaryotes

Cited by 23 publications

References 291 publications

Newly synthesized mRNA escapes translational repression during the acute phase of the mammalian unfolded protein response

Newly synthesized mRNA escapes translational repression during the acute phase of the mammalian unfolded protein response

Localization and Functional Roles of Components of the Translation Apparatus in the Eukaryotic Cell Nucleus

A translation enhancer element from black beetle virus engages yeast eIF4G1 to drive cap-independent translation initiation

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