mTOR- and LARP1-dependent regulation of TOP mRNA poly(A) tail and ribosome loading
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved..
Translation of 5' terminal oligopyrimidine (TOP) mRNAs encoding the protein synthesis machinery is strictly regulated by an amino-acid-sensing mTOR pathway. However, its regulatory mechanism remains elusive. Here, we demonstrate that TOP mRNA translation positively correlates with its poly(A) tail length under mTOR active/amino-acid-rich conditions, suggesting that TOP mRNAs are post-transcriptionally controlled by poly(A) tail-length regulation. Consistent with this, the tail length of TOP mRNAs dynamically fluctuates in response to amino acid availability. The poly(A) tail shortens under mTOR active/amino-acid-rich conditions, whereas the long-tailed TOP mRNAs accumulate under mTOR inactive/amino-acid-starved (AAS) conditions. An RNA-binding protein, LARP1, is indispensable for the process. LARP1 interacts with non-canonical poly(A) polymerases and induces post-transcriptional polyadenylation of the target. Our findings illustrate that LARP1 contributes to the selective accumulation of TOP mRNAs with long poly(A) tails under AAS, resulting in accelerated ribosomal loading onto TOP mRNAs for the resumption of translation after AAS.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:41 |
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| Enthalten in: |
Cell reports - 41(2022), 4 vom: 25. Okt., Seite 111548 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ogami, Koichi [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.10.2022 Date Revised 02.11.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2022.111548 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM348031270 |
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| 100 | 1 | |a Ogami, Koichi |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a mTOR- and LARP1-dependent regulation of TOP mRNA poly(A) tail and ribosome loading |
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| 500 | |a Date Revised 02.11.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Translation of 5' terminal oligopyrimidine (TOP) mRNAs encoding the protein synthesis machinery is strictly regulated by an amino-acid-sensing mTOR pathway. However, its regulatory mechanism remains elusive. Here, we demonstrate that TOP mRNA translation positively correlates with its poly(A) tail length under mTOR active/amino-acid-rich conditions, suggesting that TOP mRNAs are post-transcriptionally controlled by poly(A) tail-length regulation. Consistent with this, the tail length of TOP mRNAs dynamically fluctuates in response to amino acid availability. The poly(A) tail shortens under mTOR active/amino-acid-rich conditions, whereas the long-tailed TOP mRNAs accumulate under mTOR inactive/amino-acid-starved (AAS) conditions. An RNA-binding protein, LARP1, is indispensable for the process. LARP1 interacts with non-canonical poly(A) polymerases and induces post-transcriptional polyadenylation of the target. Our findings illustrate that LARP1 contributes to the selective accumulation of TOP mRNAs with long poly(A) tails under AAS, resulting in accelerated ribosomal loading onto TOP mRNAs for the resumption of translation after AAS | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CP: Molecular biology | |
| 650 | 4 | |a LARP1 | |
| 650 | 4 | |a TOP mRNA | |
| 650 | 4 | |a amino acid starvation | |
| 650 | 4 | |a deadenylation | |
| 650 | 4 | |a mTOR | |
| 650 | 4 | |a poly(A) tail | |
| 650 | 4 | |a polyadenylation | |
| 650 | 4 | |a ribosome | |
| 650 | 4 | |a translation | |
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| 650 | 7 | |a Ribonucleoproteins |2 NLM | |
| 650 | 7 | |a Autoantigens |2 NLM | |
| 650 | 7 | |a TOR Serine-Threonine Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a RNA-Binding Proteins |2 NLM | |
| 650 | 7 | |a Polynucleotide Adenylyltransferase |2 NLM | |
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| 650 | 7 | |a Amino Acids |2 NLM | |
| 700 | 1 | |a Oishi, Yuka |e verfasserin |4 aut | |
| 700 | 1 | |a Sakamoto, Kentaro |e verfasserin |4 aut | |
| 700 | 1 | |a Okumura, Mayu |e verfasserin |4 aut | |
| 700 | 1 | |a Yamagishi, Ryota |e verfasserin |4 aut | |
| 700 | 1 | |a Inoue, Takumi |e verfasserin |4 aut | |
| 700 | 1 | |a Hibino, Masaya |e verfasserin |4 aut | |
| 700 | 1 | |a Nogimori, Takuto |e verfasserin |4 aut | |
| 700 | 1 | |a Yamaguchi, Natsumi |e verfasserin |4 aut | |
| 700 | 1 | |a Furutachi, Kazuya |e verfasserin |4 aut | |
| 700 | 1 | |a Hosoda, Nao |e verfasserin |4 aut | |
| 700 | 1 | |a Inagaki, Hiroto |e verfasserin |4 aut | |
| 700 | 1 | |a Hoshino, Shin-Ichi |e verfasserin |4 aut | |
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