PMID- 25800702
OWN - NLM
STAT- MEDLINE
DCOM- 20150710
LR  - 20181113
IS  - 1432-1203 (Electronic)
IS  - 0340-6717 (Linking)
VI  - 134
IP  - 6
DP  - 2015 Jun
TI  - Analysis of human upstream open reading frames and impact on gene expression.
PG  - 605-12
LID - 10.1007/s00439-015-1544-7 [doi]
AB  - The upstream open reading frame (uORF) is a post-transcriptional regulatory 
      element in the 5' untranslated region (5'UTR), which modulates the translation 
      levels of main open reading frame (mORF). Earlier studies showed that disturbed 
      uORF-mediated translation control can result in drastic changes in translation 
      levels of mORF, leading to genetic disorders. To date, there has been no 
      systematic investigation into the relationship between variations in patients and 
      uORF status. Here, taking the advantage of several datasets, including gene 
      ontology (GO) annotations and sequence feature analysis, we have examined uORF 
      impacts in human transcripts. GO annotations indicate that uORF-containing genes 
      are enriched in certain features such as oncogenes and transcription factors. 
      Sequence feature analysis reveals that uORF is a factor for determination of the 
      translation initiation site (TIS) in human transcripts. We show that genes with 
      uORFs have lower protein expression levels than genes without uORFs in multiple 
      human tissues. Moreover, by examining three disease variation databases, we 
      identified uORF-altering mutations from a total of 3,740,225 variations, which 
      are highly suspected to be associated with changed levels of gene expression. For 
      an experimental validation, we found four mutations with significant effects on 
      protein expression but with only modest changes in transcription levels. These 
      findings will provide researchers on related diseases with new insights into the 
      importance of known mutations.
FAU - Ye, Yuhua
AU  - Ye Y
AD  - Department of Medical Genetics, School of Basic Medical Sciences, Southern 
      Medical University, Guangzhou, China.
FAU - Liang, Yidan
AU  - Liang Y
FAU - Yu, Qiuxia
AU  - Yu Q
FAU - Hu, Lingling
AU  - Hu L
FAU - Li, Haoli
AU  - Li H
FAU - Zhang, Zhenhai
AU  - Zhang Z
FAU - Xu, Xiangmin
AU  - Xu X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150324
PL  - Germany
TA  - Hum Genet
JT  - Human genetics
JID - 7613873
RN  - 0 (5' Untranslated Regions)
SB  - IM
MH  - 5' Untranslated Regions/*genetics
MH  - Cell Line
MH  - Databases, Genetic
MH  - Gene Expression Regulation/*genetics
MH  - Humans
MH  - *Mutation
MH  - Open Reading Frames/*genetics
MH  - Response Elements/*genetics
EDAT- 2015/03/25 06:00
MHDA- 2015/07/15 06:00
CRDT- 2015/03/25 06:00
PHST- 2014/12/18 00:00 [received]
PHST- 2015/03/16 00:00 [accepted]
PHST- 2015/03/25 06:00 [entrez]
PHST- 2015/03/25 06:00 [pubmed]
PHST- 2015/07/15 06:00 [medline]
AID - 10.1007/s00439-015-1544-7 [doi]
PST - ppublish
SO  - Hum Genet. 2015 Jun;134(6):605-12. doi: 10.1007/s00439-015-1544-7. Epub 2015 Mar 
      24.