Cytoplasmic mRNA decay represses RNA polymerase II transcription during early apoptosis
RNA abundance is generally sensitive to perturbations in decay and synthesis rates, but crosstalk between RNA polymerase II transcription and cytoplasmic mRNA degradation often leads to compensatory changes in gene expression. Here, we reveal that widespread mRNA decay during early apoptosis repress...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2021-06-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/58342 |
| _version_ | 1811253629098655744 |
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| author | Christopher Duncan-Lewis Ella Hartenian Valeria King Britt A Glaunsinger |
| author_facet | Christopher Duncan-Lewis Ella Hartenian Valeria King Britt A Glaunsinger |
| author_sort | Christopher Duncan-Lewis |
| collection | DOAJ |
| description | RNA abundance is generally sensitive to perturbations in decay and synthesis rates, but crosstalk between RNA polymerase II transcription and cytoplasmic mRNA degradation often leads to compensatory changes in gene expression. Here, we reveal that widespread mRNA decay during early apoptosis represses RNAPII transcription, indicative of positive (rather than compensatory) feedback. This repression requires active cytoplasmic mRNA degradation, which leads to impaired recruitment of components of the transcription preinitiation complex to promoter DNA. Importin α/β-mediated nuclear import is critical for this feedback signaling, suggesting that proteins translocating between the cytoplasm and nucleus connect mRNA decay to transcription. We also show that an analogous pathway activated by viral nucleases similarly depends on nuclear protein import. Collectively, these data demonstrate that accelerated mRNA decay leads to the repression of mRNA transcription, thereby amplifying the shutdown of gene expression. This highlights a conserved gene regulatory mechanism by which cells respond to threats. |
| first_indexed | 2024-04-12T16:53:39Z |
| format | Article |
| id | doaj.art-3f9a43cc4bbf4a76a6986258e5c17924 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:53:39Z |
| publishDate | 2021-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-3f9a43cc4bbf4a76a6986258e5c179242022-12-22T03:24:18ZengeLife Sciences Publications LtdeLife2050-084X2021-06-011010.7554/eLife.58342Cytoplasmic mRNA decay represses RNA polymerase II transcription during early apoptosisChristopher Duncan-Lewis0https://orcid.org/0000-0001-7775-5856Ella Hartenian1Valeria King2Britt A Glaunsinger3https://orcid.org/0000-0003-0479-9377Department of Molecular and Cell Biology; University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology; University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology; University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology; University of California, Berkeley, Berkeley, United States; Department of Plant and Microbial Biology; University of California, Berkeley, Berkeley, United States; Howard Hughes Medical Institute, Berkeley, Berkeley, United StatesRNA abundance is generally sensitive to perturbations in decay and synthesis rates, but crosstalk between RNA polymerase II transcription and cytoplasmic mRNA degradation often leads to compensatory changes in gene expression. Here, we reveal that widespread mRNA decay during early apoptosis represses RNAPII transcription, indicative of positive (rather than compensatory) feedback. This repression requires active cytoplasmic mRNA degradation, which leads to impaired recruitment of components of the transcription preinitiation complex to promoter DNA. Importin α/β-mediated nuclear import is critical for this feedback signaling, suggesting that proteins translocating between the cytoplasm and nucleus connect mRNA decay to transcription. We also show that an analogous pathway activated by viral nucleases similarly depends on nuclear protein import. Collectively, these data demonstrate that accelerated mRNA decay leads to the repression of mRNA transcription, thereby amplifying the shutdown of gene expression. This highlights a conserved gene regulatory mechanism by which cells respond to threats.https://elifesciences.org/articles/58342apoptosisRNA decayRNA polymerase IIfeedbackPNPT1dis3l2 |
| spellingShingle | Christopher Duncan-Lewis Ella Hartenian Valeria King Britt A Glaunsinger Cytoplasmic mRNA decay represses RNA polymerase II transcription during early apoptosis eLife apoptosis RNA decay RNA polymerase II feedback PNPT1 dis3l2 |
| title | Cytoplasmic mRNA decay represses RNA polymerase II transcription during early apoptosis |
| title_full | Cytoplasmic mRNA decay represses RNA polymerase II transcription during early apoptosis |
| title_fullStr | Cytoplasmic mRNA decay represses RNA polymerase II transcription during early apoptosis |
| title_full_unstemmed | Cytoplasmic mRNA decay represses RNA polymerase II transcription during early apoptosis |
| title_short | Cytoplasmic mRNA decay represses RNA polymerase II transcription during early apoptosis |
| title_sort | cytoplasmic mrna decay represses rna polymerase ii transcription during early apoptosis |
| topic | apoptosis RNA decay RNA polymerase II feedback PNPT1 dis3l2 |
| url | https://elifesciences.org/articles/58342 |
| work_keys_str_mv | AT christopherduncanlewis cytoplasmicmrnadecayrepressesrnapolymeraseiitranscriptionduringearlyapoptosis AT ellahartenian cytoplasmicmrnadecayrepressesrnapolymeraseiitranscriptionduringearlyapoptosis AT valeriaking cytoplasmicmrnadecayrepressesrnapolymeraseiitranscriptionduringearlyapoptosis AT brittaglaunsinger cytoplasmicmrnadecayrepressesrnapolymeraseiitranscriptionduringearlyapoptosis |