PMID- 28584194
OWN - NLM
STAT- MEDLINE
DCOM- 20170919
LR  - 20181113
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 37
IP  - 15
DP  - 2017 Aug 1
TI  - Efficient and Accurate Translation Initiation Directed by TISU Involves RPS3 and 
      RPS10e Binding and Differential Eukaryotic Initiation Factor 1A Regulation.
LID - 10.1128/MCB.00150-17 [doi]
LID - e00150-17
AB  - Canonical translation initiation involves ribosomal scanning, but short 5' 
      untranslated region (5'UTR) mRNAs are translated in a scanning-independent 
      manner. The extent and mechanism of scanning-independent translation are not 
      fully understood. Here we report that short 5'UTR mRNAs constitute a substantial 
      fraction of the translatome. Short 5'UTR mRNAs are enriched with TISU 
      (translation initiator of short 5'UTR), a 12-nucleotide element directing 
      efficient scanning-independent translation. Comprehensive mutagenesis revealed 
      that each AUG codon-flanking nucleotide of TISU contributes to translational 
      strength, but only a few are important for accuracy. Using site-specific UV 
      cross-linking of ribosomal complexes assembled on TISU mRNA, we demonstrate 
      specific binding of TISU to ribosomal proteins at the E and A sites. We 
      identified RPS3 as the major TISU binding protein in the 48S complex A site. Upon 
      80S complex formation, RPS3 interaction is weakened and switched to RPS10e 
      (formerly called RPS10). We further demonstrate that TISU is particularly 
      dependent on eukaryotic initiation factor 1A (eIF1A) which interacts with both 
      RPS3 and RPS10e. Our findings suggest that the cap-recruited ribosome 
      specifically binds the TISU nucleotides at the A and E sites in cooperation with 
      eIF1A to promote scanning arrest.
CI  - Copyright (c) 2017 American Society for Microbiology.
FAU - Haimov, Ora
AU  - Haimov O
AD  - Department of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot, 
      Israel.
FAU - Sinvani, Hadar
AU  - Sinvani H
AD  - Department of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot, 
      Israel.
FAU - Martin, Franck
AU  - Martin F
AD  - Institut de Biologie Moleculaire et Cellulaire, Architecture et Reactivite de 
      l'ARN CNRS UPR9002, Universite de Strasbourg, Strasbourg, France.
FAU - Ulitsky, Igor
AU  - Ulitsky I
AD  - Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, 
      Israel.
FAU - Emmanuel, Rafi
AU  - Emmanuel R
AD  - Emendo Biotheraputics, Ness-Ziona, Israel.
FAU - Tamarkin-Ben-Harush, Ana
AU  - Tamarkin-Ben-Harush A
AD  - Department of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot, 
      Israel.
FAU - Vardy, Assaf
AU  - Vardy A
AD  - Department of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot, 
      Israel.
FAU - Dikstein, Rivka
AU  - Dikstein R
AD  - Department of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot, 
      Israel rivka.dikstein@weizmann.ac.il.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170714
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Eukaryotic Initiation Factor-1)
RN  - 0 (RNA, Messenger)
RN  - 0 (RPS10 protein, human)
RN  - 0 (RPS3 protein, human)
RN  - 0 (Ribosomal Proteins)
RN  - 0 (eukaryotic peptide initiation factor-1A)
SB  - IM
MH  - *5' Untranslated Regions
MH  - Animals
MH  - Cell Line
MH  - Eukaryotic Initiation Factor-1/*metabolism
MH  - HEK293 Cells
MH  - HeLa Cells
MH  - Humans
MH  - Mice
MH  - Protein Binding
MH  - *Protein Biosynthesis
MH  - Protein Interaction Maps
MH  - RNA, Messenger/genetics/metabolism
MH  - Ribosomal Proteins/*metabolism
MH  - Ribosomes/genetics/metabolism
PMC - PMC5514451
OTO - NOTNLM
OT  - RPS10
OT  - RPS10e
OT  - RPS3
OT  - TISU
OT  - eIF1A
OT  - short 5'UTR
OT  - translation initiation
EDAT- 2017/06/07 06:00
MHDA- 2017/09/20 06:00
PMCR- 2018/01/14
CRDT- 2017/06/07 06:00
PHST- 2017/03/30 00:00 [received]
PHST- 2017/05/17 00:00 [accepted]
PHST- 2017/06/07 06:00 [pubmed]
PHST- 2017/09/20 06:00 [medline]
PHST- 2017/06/07 06:00 [entrez]
PHST- 2018/01/14 00:00 [pmc-release]
AID - MCB.00150-17 [pii]
AID - 00150-17 [pii]
AID - 10.1128/MCB.00150-17 [doi]
PST - epublish
SO  - Mol Cell Biol. 2017 Jul 14;37(15):e00150-17. doi: 10.1128/MCB.00150-17. Print 
      2017 Aug 1.