Cellular mRNA recruits the ribosome via eIF3-PABP bridge to initiate internal translation

RNA Biology
Nehal ThakorM Holcik

Abstract

IRES-mediated translation of key cell fate regulating genes has been implicated in tumorigenesis. Concerted action of canonical eukaryotic initiation factors and IRES transacting factors (ITAFs) was shown to regulate cellular IRES mediated translation; however, the precise molecular mechanism of ribosome recruitment to cellular IRESes remains unclear. Here we show that the X-linked inhibitor of apoptosis (XIAP) IRES operates in an evolutionary conserved viral like mode and the structural integrity, particularly in the vicinity of AUG, is critical for ribosome recruitment. The binding of eIF3 together with PABP potentiates ribosome recruitment to the IRES. Our data support the model in which eIF3 binds directly to the XIAP IRES RNA in a structure-dependent manner and acts as a scaffold for IRES RNA, PABP and the 40S ribosome.

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Citations

Apr 13, 2017·RNA Biology·Andrea Barta, Michael F Jantsch
Oct 6, 2017·Nucleic Acids Research·Leoš Shivaya ValášekStanislava Gunišová
Apr 7, 2018·Wiley Interdisciplinary Reviews. RNA·Nikolay E Shirokikh, Thomas Preiss
Nov 4, 2017·RNA Biology·Andreia Gomes-DuarteLuísa Romão
May 29, 2018·Biotechnology & Genetic Engineering Reviews·Luc Roberts, Hans-Joachim Wieden
Feb 23, 2019·International Journal of Molecular Sciences·Anne-Claire GodetAnne-Catherine Prats
Jan 14, 2017·Journal of Nucleic Acids·Divya Khandige SharmaNehal Thakor
Sep 22, 2020·Trends in Genetics : TIG·Anne Ramat, Martine Simonelig
Nov 16, 2020·Genomics·Shi-Long JiangWen-Xu Hong
Nov 17, 2020·Journal of Molecular Biology·Eleni G KaliatsiConstantinos Stathopoulos
May 12, 2021·Cellular Signalling·Lilas AlboushiSeyed Mehdi Jafarnejad
Sep 14, 2021·Frontiers in Genetics·Prakash Amruth Raj ChukkaNehal Thakor

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Methods Mentioned

BETA
toeprinting
gel mobility shift assay
restriction digest
in vitro transcription
electrophoresis
X-ray

Software Mentioned

RNASTRUCTURE

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