Quality control of transcription start site selection by nonsense-mediated-mRNA decay
Abstract
Nonsense-mediated mRNA decay (NMD) is a translation-dependent RNA quality-control pathway targeting transcripts such as messenger RNAs harboring premature stop-codons or short upstream open reading frame (uORFs). Our transcription start sites (TSSs) analysis of Saccharomyces cerevisiae cells deficient for RNA degradation pathways revealed that about half of the pervasive transcripts are degraded by NMD, which provides a fail-safe mechanism to remove spurious transcripts that escaped degradation in the nucleus. Moreover, we found that the low specificity of RNA polymerase II TSSs selection generates, for 47% of the expressed genes, NMD-sensitive transcript isoforms carrying uORFs or starting downstream of the ATG START codon. Despite the low abundance of this last category of isoforms, their presence seems to constrain genomic sequences, as suggested by the significant bias against in-frame ATGs specifically found at the beginning of the corresponding genes and reflected by a depletion of methionines in the N-terminus of the encoded proteins.
Keywords
RNA quality control
chromosomes
Codon
Nonsense
evolutionary biology
Gene Expression Regulation
Fungal
genes
genomics
non-coding RNAs
Nonsense Mediated mRNA Decay
non-sense mediated mRNA decay
nuclear RNA degradation
Open Reading Frames
RNA
Messenger
RNA Polymerase II
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
S. cerevisiae
transcription initiation
Transcription Initiation Site
Origin : Publication funded by an institution
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