PMID- 33992089
OWN - NLM
STAT- MEDLINE
DCOM- 20211116
LR  - 20211116
IS  - 2661-8850 (Electronic)
IS  - 2661-8850 (Linking)
VI  - 22
IP  - 1
DP  - 2021 May 16
TI  - Impact of uORFs in mediating regulation of translation in stress conditions.
PG  - 29
LID - 10.1186/s12860-021-00363-9 [doi]
LID - 29
AB  - BACKGROUND: A large fraction of genes contains upstream ORFs (uORFs) in the 5' 
      untranslated region (5'UTR). The translation of uORFs can inhibit the translation 
      of the main coding sequence, for example by causing premature dissociation of the 
      two ribosomal units or ribosome stalling. However, it is currently unknown if 
      most uORFs are inhibitory or if this activity is restricted to specific cases. 
      Here we interrogate ribosome profiling data from three different stress 
      experiments in yeast to gain novel insights into this question. RESULTS: By 
      comparing ribosome occupancies in different conditions and experiments we obtain 
      strong evidence that, in comparison to primary coding sequences (CDS), which 
      undergo translational arrest during stress, the translation of uORFs is mostly 
      unaffected by changes in the environment. As a result, the relative abundance of 
      uORF-encoded peptides increases during stress. In general, the changes in the 
      translational efficiency of regions containing uORFs do not seem to affect 
      downstream translation. The exception are uORFs found in a subset of genes that 
      are significantly up-regulated at the level of translation during stress; these 
      uORFs tend to be translated at lower levels in stress conditions than in optimal 
      growth conditions, facilitating the translation of the CDS during stress. We find 
      new examples of uORF-mediated regulation of translation, including the Gcn4 
      functional homologue fil1 and ubi4 genes in S. pombe. CONCLUSION: We find 
      evidence that the relative amount of uORF-encoded peptides increases during 
      stress. The increased translation of uORFs is however uncoupled from the general 
      CDS translational repression observed during stress. In a subset of genes that 
      encode proteins that need to be rapidly synthesized upon stress uORFs act as 
      translational switches.
FAU - Moro, Simone G
AU  - Moro SG
AD  - Evolutionary Genomics Group, Research Programme on Biomedical Informatics, 
      Hospital del Mar Medical Research Institute (IMIM) and Universitat Pompeu Fabra 
      (UPF), Barcelona, Spain.
FAU - Hermans, Cedric
AU  - Hermans C
AD  - Bioinformatics Knowledge Center, Howest University of Applied Sciences, Bruges, 
      Belgium.
FAU - Ruiz-Orera, Jorge
AU  - Ruiz-Orera J
AD  - Cardiovascular and Metabolic Sciences, Max Delbruck Center for Molecular Medicine 
      in the Helmholtz Association (MDC), Berlin, Germany.
FAU - Alba, M Mar
AU  - Alba MM
AD  - Evolutionary Genomics Group, Research Programme on Biomedical Informatics, 
      Hospital del Mar Medical Research Institute (IMIM) and Universitat Pompeu Fabra 
      (UPF), Barcelona, Spain. malba@imim.es.
AD  - Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain. 
      malba@imim.es.
LA  - eng
PT  - Journal Article
DEP - 20210516
PL  - England
TA  - BMC Mol Cell Biol
JT  - BMC molecular and cell biology
JID - 101741148
RN  - 0 (3' Untranslated Regions)
SB  - IM
MH  - 3' Untranslated Regions
MH  - *Gene Expression Regulation, Fungal
MH  - *Open Reading Frames
MH  - *Protein Biosynthesis
MH  - Saccharomyces cerevisiae/genetics
MH  - Schizosaccharomyces/genetics
MH  - Stress, Physiological/*genetics
PMC - PMC8126119
COIS- The authors declare no competing interests.
EDAT- 2021/05/17 06:00
MHDA- 2021/11/17 06:00
PMCR- 2021/05/16
CRDT- 2021/05/16 20:22
PHST- 2021/02/12 00:00 [received]
PHST- 2021/04/05 00:00 [accepted]
PHST- 2021/05/16 20:22 [entrez]
PHST- 2021/05/17 06:00 [pubmed]
PHST- 2021/11/17 06:00 [medline]
PHST- 2021/05/16 00:00 [pmc-release]
AID - 10.1186/s12860-021-00363-9 [pii]
AID - 363 [pii]
AID - 10.1186/s12860-021-00363-9 [doi]
PST - epublish
SO  - BMC Mol Cell Biol. 2021 May 16;22(1):29. doi: 10.1186/s12860-021-00363-9.