PMID- 37013984
OWN - NLM
STAT- MEDLINE
DCOM- 20230601
LR  - 20230601
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 51
IP  - 9
DP  - 2023 May 22
TI  - Translation regulation of specific mRNAs by RPS26 C-terminal RNA-binding tail 
      integrates energy metabolism and AMPK-mTOR signaling.
PG  - 4415-4428
LID - 10.1093/nar/gkad238 [doi]
AB  - Increasing evidence suggests that ribosome composition and modifications 
      contribute to translation control. Whether direct mRNA binding by ribosomal 
      proteins regulates the translation of specific mRNA and contributes to ribosome 
      specialization has been poorly investigated. Here, we used CRISPR-Cas9 to mutate 
      the RPS26 C-terminus (RPS26dC) predicted to bind AUG upstream nucleotides at the 
      exit channel. RPS26 binding to positions -10 to -16 of short 5' untranslated 
      region (5'UTR) mRNAs exerts positive and negative effects on translation directed 
      by Kozak and Translation Initiator of Short 5'UTR (TISU), respectively. 
      Consistent with that, shortening the 5'UTR from 16 to 10 nt diminished Kozak and 
      enhanced TISU-driven translation. As TISU is resistant and Kozak is sensitive to 
      energy stress, we examined stress responses and found that the RPS26dC mutation 
      confers resistance to glucose starvation and mTOR inhibition. Furthermore, the 
      basal mTOR activity is reduced while AMP-activated protein kinase is activated in 
      RPS26dC cells, mirroring energy-deprived wild-type (WT) cells. Likewise, the 
      translatome of RPS26dC cells is correlated to glucose-starved WT cells. Our 
      findings uncover the central roles of RPS26 C-terminal RNA binding in energy 
      metabolism, in the translation of mRNAs bearing specific features and in the 
      translation tolerance of TISU genes to energy stress.
CI  - (c) The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic 
      Acids Research.
FAU - Havkin-Solomon, Tal
AU  - Havkin-Solomon T
AD  - Department of Biomolecular Sciences, The Weizmann Institute of Science, 
      Rehovot 7610001, Israel.
FAU - Fraticelli, Davide
AU  - Fraticelli D
AD  - Department of Biomolecular Sciences, The Weizmann Institute of Science, 
      Rehovot 7610001, Israel.
FAU - Bahat, Anat
AU  - Bahat A
AD  - Department of Biomolecular Sciences, The Weizmann Institute of Science, 
      Rehovot 7610001, Israel.
FAU - Hayat, Daniel
AU  - Hayat D
AD  - Department of Biomolecular Sciences, The Weizmann Institute of Science, 
      Rehovot 7610001, Israel.
FAU - Reuven, Nina
AU  - Reuven N
AUID- ORCID: 0000-0003-1569-3818
AD  - Department of Molecular Genetics, The Weizmann Institute of Science, 
      Rehovot 7610001, Israel.
FAU - Shaul, Yosef
AU  - Shaul Y
AD  - Department of Molecular Genetics, The Weizmann Institute of Science, 
      Rehovot 7610001, Israel.
FAU - Dikstein, Rivka
AU  - Dikstein R
AUID- ORCID: 0000-0002-6251-4723
AD  - Department of Biomolecular Sciences, The Weizmann Institute of Science, 
      Rehovot 7610001, Israel.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (5' Untranslated Regions)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - 0 (Ribosomal Proteins)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
CIN - 10.1093/nar/gkad269
MH  - 5' Untranslated Regions
MH  - *AMP-Activated Protein Kinases/genetics/metabolism
MH  - Energy Metabolism/genetics
MH  - Protein Biosynthesis
MH  - *Ribosomal Proteins/genetics/metabolism
MH  - RNA, Messenger/metabolism
MH  - *TOR Serine-Threonine Kinases/genetics/metabolism
PMC - PMC10201367
EDAT- 2023/04/05 06:00
MHDA- 2023/05/23 06:42
PMCR- 2023/04/04
CRDT- 2023/04/04 07:22
PHST- 2023/03/31 00:00 [accepted]
PHST- 2023/02/16 00:00 [revised]
PHST- 2022/10/20 00:00 [received]
PHST- 2023/05/23 06:42 [medline]
PHST- 2023/04/05 06:00 [pubmed]
PHST- 2023/04/04 07:22 [entrez]
PHST- 2023/04/04 00:00 [pmc-release]
AID - 7103205 [pii]
AID - gkad238 [pii]
AID - 10.1093/nar/gkad238 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2023 May 22;51(9):4415-4428. doi: 10.1093/nar/gkad238.