scholarly journals Functional interaction between the RNA exosome and the sirtuin deacetylase Hst3 maintains transcriptional homeostasis

2021 ◽  
Author(s):  
Alysia R. Bryll ◽  
Craig L. Peterson

Eukaryotic cells maintain an optimal level of mRNAs through unknown mechanisms that balance RNA synthesis and degradation. We found that inactivation of the RNA exosome leads to global reduction of nascent mRNA transcripts, and that this defect is accentuated by loss of deposition of histone variant H2A.Z. We identify the mRNA for the sirtuin deacetylase Hst3 as a key target for the RNA exosome that mediates communication between RNA degradation and transcription machineries. These findings reveal how the RNA exosome and H2A.Z function together to control a deacetylase, ensuring proper levels of transcription in response to changes in RNA degradation.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shiho Makino ◽  
Tomoko Kawamata ◽  
Shintaro Iwasaki ◽  
Yoshinori Ohsumi

AbstractSynthesis and degradation of cellular constituents must be balanced to maintain cellular homeostasis, especially during adaptation to environmental stress. The role of autophagy in the degradation of proteins and organelles is well-characterized. However, autophagy-mediated RNA degradation in response to stress and the potential preference of specific RNAs to undergo autophagy-mediated degradation have not been examined. In this study, we demonstrate selective mRNA degradation by rapamycin-induced autophagy in yeast. Profiling of mRNAs from the vacuole reveals that subsets of mRNAs, such as those encoding amino acid biosynthesis and ribosomal proteins, are preferentially delivered to the vacuole by autophagy for degradation. We also reveal that autophagy-mediated mRNA degradation is tightly coupled with translation by ribosomes. Genome-wide ribosome profiling suggested a high correspondence between ribosome association and targeting to the vacuole. We propose that autophagy-mediated mRNA degradation is a unique and previously-unappreciated function of autophagy that affords post-transcriptional gene regulation.


2021 ◽  
Author(s):  
Fabio Chizzolini ◽  
Alexandra Kent ◽  
Luiz F. M. Passalacqua ◽  
Andrej Lupták

<p>A mechanism of nucleoside triphosphorylation would have been critical in an evolving “RNA world” to provide high-energy substrates for reactions such as RNA polymerization. However, synthetic approaches to produce ribonucleoside triphosphoates (rNTPs) have suffered from conditions such as high temperatures or high pH that lead to increased RNA degradation, as well as substrate production that cannot sustain replication. We demonstrate that cyclic trimetaphosphate (cTmp) can react with nucleosides to form rNTPs under mild, prebiotically-relevant conditions, with second-order rate constants ranging from 1.7 x 10<sup>–6</sup> to 6.5 x 10<sup>–6</sup> M<sup>–1</sup> s<sup>–1</sup>. The ATP reaction shows a linear dependence on pH and Mg<sup>2+</sup>, and an enthalpy of activation of 88 ± 4 kJ/mol. At millimolar nucleoside and cTmp concentrations, the rNTP production rate is sufficient to facilitate RNA synthesis by both T7 RNA polymerase and a polymerase ribozyme. We suggest that the optimized reaction of cTmp with nucleosides may provide a viable connection between prebiotic nucleotide synthesis and RNA replication.</p>


1978 ◽  
Vol 176 (3) ◽  
pp. 933-941 ◽  
Author(s):  
W T Melvin ◽  
H M Keir

When BHK-21/C13 cells growing exponentially in 10% serum are transferred to a medium containing only 0.25% serum, cell growth is decreased. After initial changes in RNA synthesis and degradation, protein content of the cultures reaches a plateau and eventually DNA synthesis is arrested. rRNA is relatively stable in exponentially growing cells. Immediately after ‘step-down’ rRNA degradation commences, but poly(A)-containing RNA does not appear to be degraded any faster than in control cells. Reutilization of RNA precursors has been independently measured and amounts to less than 1%/h for rRNA, insufficient to influence the conclusion that rRNA degradation begins almost immediately after ‘step-down’. The degree of reutilization of uridine is much greater for poly(A)-containing RNA than for poly(A)-free RNA.


2020 ◽  
Vol 31 (21) ◽  
pp. 2398-2408
Author(s):  
Manisha Sharma ◽  
Susan R. Wente

We uncovered a nuclear role for human Gle1 in coordinating transcription termination. When nucleocytoplasmic shuttling of Gle1 is disrupted, nascent mRNA transcripts are elongated. Gle1 colocalizes with DDX1, and loss of Gle1 shuttling impairs recruitment of DDX1 to CstF-64 and transcription termination foci, leading to improper pre-mRNA cleavage.


2010 ◽  
Vol 38 (6) ◽  
pp. 1506-1510 ◽  
Author(s):  
Boris Reznik ◽  
Jens Lykke-Andersen

Gene expression can be regulated at multiple levels, including transcription, RNA processing, RNA localization, translation and, finally, RNA turnover. RNA degradation may occur at points along the processing pathway or during translation as it undergoes quality control by RNA surveillance systems. Alternatively, mRNAs may be subject to regulated degradation, often mediated by cis-encoded determinants in the mRNA sequence that, through the recruitment of trans factors, determine the fate of the mRNA. The aim of the present review is to highlight mechanisms of regulated and quality-control RNA degradation in eukaryotic cells, with an emphasis on mammals.


2017 ◽  
Vol 37 (18) ◽  
Author(s):  
Jonathan Merran ◽  
Jeffry L. Corden

ABSTRACT Termination of Saccharomyces cerevisiae RNA polymerase II (Pol II) transcripts occurs through two alternative pathways. Termination of mRNAs is coupled to cleavage and polyadenylation while noncoding transcripts are terminated through the Nrd1-Nab3-Sen1 (NNS) pathway in a process that is linked to RNA degradation by the nuclear exosome. Some mRNA transcripts are also attenuated through premature termination directed by the NNS complex. In this paper we present the results of nuclear depletion of the NNS component Nab3. As expected, many noncoding RNAs fail to terminate properly. In addition, we observe that nitrogen catabolite-repressed genes are upregulated by Nab3 depletion.


2006 ◽  
Vol 17 (3) ◽  
pp. 1184-1193 ◽  
Author(s):  
Agata T. Rogowska ◽  
Olga Puchta ◽  
Anna M. Czarnecka ◽  
Aneta Kaniak ◽  
Piotr P. Stepien ◽  
...  

The Saccharomyces cerevisiae SUV3 gene encodes the helicase component of the mitochondrial degradosome (mtEXO), the principal 3′-to-5′ exoribonuclease of yeast mitochondria responsible for RNA turnover and surveillance. Inactivation of SUV3 (suv3Δ) causes multiple defects related to overaccumulation of aberrant transcripts and precursors, leading to a disruption of mitochondrial gene expression and loss of respiratory function. We isolated spontaneous suppressors that partially restore mitochondrial function in suv3Δ strains devoid of mitochondrial introns and found that they correspond to partial loss-of-function mutations in genes encoding the two subunits of the mitochondrial RNA polymerase (Rpo41p and Mtf1p) that severely reduce the transcription rate in mitochondria. These results show that reducing the transcription rate rescues defects in RNA turnover and demonstrates directly the vital importance of maintaining the balance between RNA synthesis and degradation.


2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Natalia Sikorska ◽  
Hélène Zuber ◽  
Anthony Gobert ◽  
Heike Lange ◽  
Dominique Gagliardi

2021 ◽  
Author(s):  
Fabio Chizzolini ◽  
Alexandra Kent ◽  
Luiz F. M. Passalacqua ◽  
Andrej Lupták

<p>A mechanism of nucleoside triphosphorylation would have been critical in an evolving “RNA world” to provide high-energy substrates for reactions such as RNA polymerization. However, synthetic approaches to produce ribonucleoside triphosphoates (rNTPs) have suffered from conditions such as high temperatures or high pH that lead to increased RNA degradation, as well as substrate production that cannot sustain replication. We demonstrate that cyclic trimetaphosphate (cTmp) can react with nucleosides to form rNTPs under mild, prebiotically-relevant conditions, with second-order rate constants ranging from 1.7 x 10<sup>–6</sup> to 6.5 x 10<sup>–6</sup> M<sup>–1</sup> s<sup>–1</sup>. The ATP reaction shows a linear dependence on pH and Mg<sup>2+</sup>, and an enthalpy of activation of 88 ± 4 kJ/mol. At millimolar nucleoside and cTmp concentrations, the rNTP production rate is sufficient to facilitate RNA synthesis by both T7 RNA polymerase and a polymerase ribozyme. We suggest that the optimized reaction of cTmp with nucleosides may provide a viable connection between prebiotic nucleotide synthesis and RNA replication.</p>


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