RNA-controlled nucleocytoplasmic shuttling of mRNA decay factors regulates mRNA synthesis and a novel mRNA decay pathway

Shiladitya Chattopadhyay, Jose Garcia-Martinez, Gal Haimovich, Jonathan Fischer, Aya Khwaja, Oren Barkai, Silvia Gabriela Chuartzman, Maya Schuldiner, Ron Elran, Miriam I. Rosenberg, Shira Urim, Shubham Deshmukh, Katherine E. Bohnsack, Markus T. Bohnsack, Jose E. Perez-Ortin, Mordechai Choder*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

mRNA level is controlled by factors that mediate both mRNA synthesis and decay, including the 5’ to 3’ exonuclease Xrn1. Here we show that nucleocytoplasmic shuttling of several yeast mRNA decay factors plays a key role in determining both mRNA synthesis and decay. Shuttling is regulated by RNA-controlled binding of the karyopherin Kap120 to two nuclear localization sequences (NLSs) in Xrn1, location of one of which is conserved from yeast to human. The decaying RNA binds and masks NLS1, establishing a link between mRNA decay and Xrn1 shuttling. Preventing Xrn1 import, either by deleting KAP120 or mutating the two Xrn1 NLSs, compromises transcription and, unexpectedly, also cytoplasmic decay, uncovering a cytoplasmic decay pathway that initiates in the nucleus. Most mRNAs are degraded by both pathways - the ratio between them represents a full spectrum. Importantly, Xrn1 shuttling is required for proper responses to environmental changes, e.g., fluctuating temperatures, involving proper changes in mRNA abundance and in cell proliferation rate.

Original languageAmerican English
Article number7184
JournalNature Communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

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