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

Abstract

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.

Control of mRNA Stability in Fungi by NMD, EJC and CBC Factors Through 3′UTR Introns

“…With respect to the EJC and NMD mutants, this circuit might be disrupted or there might be additional transcriptional induction independent of an intact feedback circuit. The existence of such feedback circuits that connect RNA stability and transcription has been demonstrated in S. cerevisiae through the functions of XRN1 (Haimovich et al 2013).…”

“…Taken together, these data show that CBC factors are important for producing mRNP that is permissive for EJC-mediated, but not uORF-mediated, NMD. It is increasingly apparent that the nuclear history of a transcript can define its fate in the cytoplasm (Trcek et al 2011;Haimovich et al 2013;Zid and O'Shea 2014), and regardless of whether the CBC or eIF4E is associated with the mRNA at the onset of decay, CBC appears essential for EJC-mediated NMD. Thus, the CBC is critical for licensing EJC-mediated NMD.…”

“…With respect to the EJC and NMD mutants, this circuit might be disrupted or there might be additional transcriptional induction independent of an intact feedback circuit. The existence of such feedback circuits that connect RNA stability and transcription has been demonstrated in S. cerevisiae through the functions of XRN1 (Haimovich et al 2013).All of the viable deletion mutations affecting NMD, EJC, and CBC components displayed asexual growth phenotypes. Some of these mutants also had defects in their sexual development: the Dy14, Dmago, and Dupf2 strains are female sterile.…”

Growth rate controls mRNA turnover in steady and non-steady states

“…We and others have demonstrated the existence of a feedback mechanism between mRNA decay and transcription, supported by the capacity of the mRNA degradation machinery to enter the nucleus and associate with the transcription machinery in transcribed genes. 22,23 Another regulatory connection between transcription and mRNA decay, but in the direction from nucleus (transcription) to cytoplasm, has also been established since mRNAs can be co-transcriptionally bound by factors that imprint them and influence their stability and translatability. 24,25 The disruption of the mechanistic coupling between transcription and mRNA degradation helps to explain the regulation of the mRNAs that do change with growth (Fig.…”

18 Embryo Aggregation in Pig Improves Cloning Efficiency and Embryo Quality

“…Bcl-xl, an anti apoptotic associated gene in cloned pig aggregated embryos was extremely low and could not be detected in 40 cycles of RT-qPCR and Bax (pro apoptotic associated gene) expression was significantly increased. mRNA degradation is controlled by rates of synthesis and of decay [41]. However, recent results indicate that numerous untranslated mRNAs are assembled into "P bodies", this consist in numerous messenger ribonucleoproteins that could accumulate in cytoplasmic foci and can be also degraded or return to translation [42][43][44][45].…”