mRNA with Mammalian Codon Bias Accumulates in Yeast Mutants with Constitutive Stress Granules

Abstract

Stress granules and P bodies are cytoplasmic structures assembled in response to various stress factors and represent sites of temporary storage or decay of mRNAs. Depending on the source of stress, the formation of these structures may be driven by distinct mechanisms, but several stresses have been shown to stabilize mRNAs via inhibition of deadenylation. A recent study identified yeast gene deletion mutants with constitutive stress granules and elevated P bodies; however, the mechanisms which trigger its formation remain poorly understood. Here, we investigate the possibility of accumulating mRNA with mammalian codon bias, which we termed the model RNA, in these mutants. We found that the model RNA accumulates in dcp2 and xrn1 mutants and in four mutants with constitutive stress granules overlapping with P bodies. However, in eight other mutants with constitutive stress granules, the model RNA is downregulated, or its steady state levels vary. We further suggest that the accumulation of the model RNA is linked to its protection from the main mRNA surveillance path. However, there is no obvious targeting of the model RNA to stress granules or P bodies. Thus, accumulation of the model RNA and formation of constitutive stress granules occur independently and only some paths inducing formation of constitutive stress granules will stabilize mRNA as well.

Yeast stress granules at a glance

“…TT foci formed in the absence of THO/TREX-2 were, but are no longer considered to be "constitutive stress granules". Further studies have revealed that, in contrast to genuine SGs, TT foci were formed by a distinct mechanism and, similar to REGs, they contain aberrant mRNPs (see Box 6), which have been exported from the nucleus (Eshleman et al, 2016;Kozlova et al, 2020).…”

Identification and validation of N7‐methylguanosine‐associated gene NCBP1 as prognostic and immune‐associated biomarkers in breast cancer patients

“… 6 , 7 , 8 Human malignancies are linked to epigenetic alterations in RNA that aren't properly controlled. m7G has been identified to take a significant role in BC in previous research, and several genes, such as NSUN2 9 and the METTL1 gene, 10 are known to adversely regulate m7G. METTL1 methyltransferase mediates m7G methylation within let‐7e miRNA, activating the let‐7e miRNA/HMGA2 axis which was linked with a poor prognosis.…”

“…METTL1 methyltransferase mediates m7G methylation within let‐7e miRNA, activating the let‐7e miRNA/HMGA2 axis which was linked with a poor prognosis. Meanwhile, other m7G‐related genes, such as DCP2 10 and DCPS, may cause illness by committing the transcript to destruction. However, it is unclear if these m7G‐regulated genes are associated with the prognosis of BC samples.…”

RNA Regulatory Networks 2.0

“…This Special Issue is concluded by two experimental papers describing how DNA methylation can be a source of variability in the expression of rRNA genes [26] and how codon bias can be a triggering factor for the accumulation of specific mRNAs into stress bodies in yeast [27]. Both articles are prime examples of how genomic variability can alter the structure and function of RNA regulatory networks.…”