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

• Published in: Nature communications Vol. 13; no. 1; p. 7184
• Main Authors: Chattopadhyay, Shiladitya, Garcia-Martinez, Jose, Haimovich, Gal, Fischer, Jonathan, Khwaja, Aya, Barkai, Oren, Chuartzman, Silvia Gabriela, Schuldiner, Maya, Elran, Ron, Rosenberg, Miriam I., Urim, Shira, Deshmukh, Shubham, Bohnsack, Katherine E., Bohnsack, Markus T., Perez-Ortin, Jose E., Choder, Mordechai
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23-11-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 38/39; 38/90; 38/91; 49/31; 631/337; 631/337/1645/2020; Cell proliferation; Decay; Environmental changes; Exonuclease; Humanities and Social Sciences; Humans; Localization; mRNA turnover; multidisciplinary; RNA - metabolism; RNA Stability; RNA, Messenger - genetics; RNA, Messenger - metabolism; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Science; Science (multidisciplinary); Synthesis; Transcription; Transcription factors; Transcription, Genetic; Yeast; Yeasts
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-34417-z

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.
Nucleocytoplasmic shuttling of several yeast mRNA decay factors regulates transcription and initiates a novel mRNA decay pathway; shuttling is controlled by the decaying RNA and is critical for coping with environmental changes.