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Gene Expression Is Circular: Factors for mRNA Degradation Also Foster mRNA Synthesis

Haimovich, Gal, Medina, Daniel A., Causse, Sebastien Z., Garber, Manuel, Millán-Zambrano, Gonzalo, Barkai, Oren, Chávez, Sebastián, Pérez-Ortín, José E., Darzacq, Xavier, Choder, Mordechai
Cell 2013 v.153 pp. 1000-1011
cytoplasm, gene expression, gene expression regulation, messenger RNA, yeasts
Maintaining proper mRNA levels is a key aspect in the regulation of gene expression. The balance between mRNA synthesis and decay determines these levels. We demonstrate that most yeast mRNAs are degraded by the cytoplasmic 5′-to-3′ pathway (the “decaysome”), as proposed previously. Unexpectedly, the level of these mRNAs is highly robust to perturbations in this major pathway because defects in various decaysome components lead to transcription downregulation. Moreover, these components shuttle between the cytoplasm and the nucleus, in a manner dependent on proper mRNA degradation. In the nucleus, they associate with chromatin—preferentially ∼30 bp upstream of transcription start-sites—and directly stimulate transcription initiation and elongation. The nuclear role of the decaysome in transcription is linked to its cytoplasmic role in mRNA decay; linkage, in turn, seems to depend on proper shuttling of its components. The gene expression process is therefore circular, whereby the hitherto first and last stages are interconnected.