An Independently folding RNA G-quadruplex domain directly recruits the 40S ribosomal subunit

Biochemistry
Debmalya BhattacharyyaSoumitra Basu

Abstract

In this study, we report that a 17-nucleotide independently folding RNA G-quadruplex (GQ) domain within the 294-nucleotide human VEGF IRES A interacts with the 40S ribosomal subunit. Footprinting and structure mapping analyses indicate that the RNA GQ forms independently and interacts directly with the 40S ribosomal subunit in the absence of other protein factors. Moreover, a filter binding assay in conjunction with enzymatic footprinting clearly established that the GQ-forming domain singularly dictates the binding affinity and also the function of internal ribosomal entry site (IRES) A. The deletion of the GQ domain abrogates the binding of the 40S ribosomal subunit to the IRES, which impairs cap-independent translation initiation. The findings provide a unique and defined role for a noncanonical RNA structure in cap-independent translation initiation by cellular IRESs. The GQ structure when present in an IRES acts as an essential element in contrast to their generally accepted inhibitory role in translation. The results of this study explain the hitherto unknown mechanistic necessity of the GQ structure in IRES function.

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Citations

Sep 27, 2016·Frontiers in Chemistry·Debmalya BhattacharyyaSoumitra Basu
Apr 7, 2018·Wiley Interdisciplinary Reviews. RNA·Nikolay E Shirokikh, Thomas Preiss
Nov 23, 2017·Nature Reviews. Molecular Cell Biology·Kathrin LeppekMaria Barna
Sep 13, 2019·Wiley Interdisciplinary Reviews. RNA·Prakash KharelSoumitra Basu
Apr 22, 2020·Nature Reviews. Molecular Cell Biology·Dhaval VarshneyShankar Balasubramanian
Jun 18, 2020·International Journal of Molecular Sciences·Chiara Reina, Vincenzo Cavalieri
Mar 28, 2021·Nucleic Acids Research·Kaixin LyuChun Kit Kwok
Apr 7, 2021·Cell Chemical Biology·Martina Zafferani, Amanda E Hargrove
Apr 28, 2021·The FEBS Journal·John W Cave, Dianna E Willis

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