Ribosomes modulate transcriptome abundance via generalized frameshift and out-of-frame mRNA decay.

• Cells need to adapt their transcriptome to quickly match cellular needs in changing environments. mRNA abundance can be controlled by altering both its synthesis and decay. Here, we show how, in response to poor nutritional conditions, the bulk of the S. cerevisiae transcriptome undergoes -1 ribosome frameshifts and experiences an accelerated out-of-frame co-translational mRNA decay. Using RNA metabolic labeling, we demonstrate that in poor nutritional conditions, nonsense-mediated mRNA decay (NMD)-dependent degradation represents at least one-third of the total mRNA decay. We further characterize this mechanism and identify low codon optimality as a key factor for ribosomes to induce out-of-frame mRNA decay. Finally, we show that this phenomenon is conserved from bacteria to humans. Our work provides evidence for a direct regulatory feedback mechanism coupling protein demand with the control of mRNA abundance to limit cellular growth and broadens the functional landscape of mRNA quality control.

Ämnesord

NATURVETENSKAP  -- Biologi -- Molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Molecular Biology (hsv//eng)

NATURVETENSKAP  -- Biologi -- Genetik och genomik (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Genetics and Genomics (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk bioinformatik och systembiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Bioinformatics and Systems Biology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)

NATURVETENSKAP  -- Biologi -- Utvecklingsbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Developmental Biology (hsv//eng)

Nyckelord

Saccharomyces cerevisiae

genetics

metabolism

growth & development

Ribosomes

genetics

metabolism

Transcriptome

RNA

Messenger

genetics

metabolism

Nonsense Mediated mRNA Decay

Saccharomyces cerevisiae Proteins

genetics

metabolism

Gene Expression Regulation

Fungal

RNA

Fungal

genetics

metabolism

RNA Stability

Humans

Frameshifting

Ribosomal

Protein Biosynthesis

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)