PMID- 36223745
OWN - NLM
STAT- MEDLINE
DCOM- 20221014
LR  - 20221029
IS  - 2211-1247 (Electronic)
VI  - 41
IP  - 2
DP  - 2022 Oct 11
TI  - An unusual mode of baseline translation adjusts cellular protein synthesis 
      capacity to metabolic needs.
PG  - 111467
LID - S2211-1247(22)01317-1 [pii]
LID - 10.1016/j.celrep.2022.111467 [doi]
AB  - In all domains of life, mechanisms exist that adjust translational capacity to 
      nutrient restriction and other growth constraints. The mammalian target of 
      rapamycin (mTOR) regulates the synthesis of ribosomal proteins and translation 
      factors in mammalian cells via phosphorylation of the La-related protein 1 
      (LARP1). In the present model of starvation-induced translational silencing, 
      LARP1 targets mRNAs carrying a 5' terminal oligopyrimidine (5'TOP) motif to shift 
      these into subpolysomal ribonucleoprotein particles. However, how these mRNAs 
      would be protected from degradation and rapidly made available to restore 
      translation capacity when needed remained enigmatic. Here, to address this, we 
      employ gradient profiling by sequencing (Grad-seq) and monosome footprinting. 
      Challenging the above model, we find that 5'TOP mRNAs, instead of being 
      translationally silenced during starvation, undergo low baseline translation with 
      reduced initiation rates. This mode of regulation ensures a stable 5'TOP mRNA 
      population under starvation and allows fast reversibility of the translational 
      repression.
CI  - Copyright (c) 2022 University of Wuerzburg. Published by Elsevier Inc. All rights 
      reserved.
FAU - Schneider, Cornelius
AU  - Schneider C
AD  - Department of Biochemistry, Theodor Boveri Institute, University of Wurzburg, 
      97074 Wurzburg, Germany; Institute for Molecular Infection Biology, University of 
      Wurzburg, 97080 Wurzburg, Germany.
FAU - Erhard, Florian
AU  - Erhard F
AD  - Institute for Virology and Immunology, University of Wurzburg, 97080 Wurzburg, 
      Germany.
FAU - Binotti, Beyenech
AU  - Binotti B
AD  - Department of Biochemistry, Theodor Boveri Institute, University of Wurzburg, 
      97074 Wurzburg, Germany.
FAU - Buchberger, Alexander
AU  - Buchberger A
AD  - Department of Biochemistry, Theodor Boveri Institute, University of Wurzburg, 
      97074 Wurzburg, Germany.
FAU - Vogel, Jorg
AU  - Vogel J
AD  - Institute for Molecular Infection Biology, University of Wurzburg, 97080 
      Wurzburg, Germany; Helmholtz Institute for RNA-based Infection Research (HIRI), 
      Helmholtz Center for Infection Research (HZI), 97080 Wurzburg, Germany. 
      Electronic address: joerg.vogel@uni-wuerzburg.de.
FAU - Fischer, Utz
AU  - Fischer U
AD  - Department of Biochemistry, Theodor Boveri Institute, University of Wurzburg, 
      97074 Wurzburg, Germany; Helmholtz Institute for RNA-based Infection Research 
      (HIRI), Helmholtz Center for Infection Research (HZI), 97080 Wurzburg, Germany. 
      Electronic address: utz.fischer@biozentrum.uni-wuerzburg.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (RNA, Messenger)
RN  - 0 (Ribonucleoproteins)
RN  - 0 (Ribosomal Proteins)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - *Protein Biosynthesis
MH  - RNA, Messenger/genetics/metabolism
MH  - Ribonucleoproteins/metabolism
MH  - Ribosomal Proteins/metabolism
MH  - *TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - 5'TOP
OT  - CP: Molecular biology
OT  - LARP1
OT  - TOP mRNAs
OT  - TOP response
OT  - baseline translation
OT  - mRNA
OT  - mTORC1
OT  - starvation
OT  - translation initiation
OT  - translation regulation
COIS- Declaration of interests The authors declare no competing interests.
EDAT- 2022/10/13 06:00
MHDA- 2022/10/15 06:00
CRDT- 2022/10/12 18:23
PHST- 2022/02/10 00:00 [received]
PHST- 2022/06/14 00:00 [revised]
PHST- 2022/09/16 00:00 [accepted]
PHST- 2022/10/12 18:23 [entrez]
PHST- 2022/10/13 06:00 [pubmed]
PHST- 2022/10/15 06:00 [medline]
AID - S2211-1247(22)01317-1 [pii]
AID - 10.1016/j.celrep.2022.111467 [doi]
PST - ppublish
SO  - Cell Rep. 2022 Oct 11;41(2):111467. doi: 10.1016/j.celrep.2022.111467.