Abstract
AbstractmRNA 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.
Funder
Israel Academy of Sciences and Humanities
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference73 articles.
1. Begley, V. et al. The mRNA degradation factor Xrn1 regulates transcription elongation in parallel to Ccr4. Nucleic Acids Res 47, 9524–9541 (2019).
2. Fischer, J. et al. The yeast exoribonuclease Xrn1 and associated factors modulate RNA polymerase II processivity in 5’ and 3’ gene regions. J. Biol. Chem. 295, 11435–11454 (2020).
3. Haimovich, G. et al. Gene Expression Is Circular: Factors for mRNA Degradation Also Foster mRNA Synthesis. Cell 153, 1000–1011 (2013).
4. Hartenian, E. & Glaunsinger, B. A. Feedback to the central dogma: cytoplasmic mRNA decay and transcription are interdependent processes. Crit. Rev. Biochem. Mol. Biol. 0, 1–14 (2019).
5. Sun, M. et al. Global analysis of Eukaryotic mRNA degradation reveals Xrn1-dependent buffering of transcript levels. Mol. Cell 52, 52–62 (2013).
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