PMID- 24260526
OWN - NLM
STAT- MEDLINE
DCOM- 20140630
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 11
DP  - 2013
TI  - Multiple transcripts from a 3'-UTR reporter vary in sensitivity to 
      nonsense-mediated mRNA decay in Saccharomyces cerevisiae.
PG  - e80981
LID - 10.1371/journal.pone.0080981 [doi]
LID - e80981
AB  - Nonsense-mediated mRNA decay (NMD) causes accelerated transcript degradation when 
      a premature translation termination codon disrupts the open reading frame (ORF). 
      Although endogenous transcripts that have uninterrupted ORFs are typically 
      insensitive to NMD, some can nonetheless become prone to NMD when translation 
      terminates at out-of-frame premature stop codons. This occurs when introns 
      containing stop codons fail to be spliced, when translation of an upstream ORF 
      (uORF) terminates in the 5'-untranslated region (5'-UTR) or the coding region, or 
      when the 5'-proximal AUG initiation codon is bypassed and translation initiates 
      at a downstream out-of-frame AUG followed by a stop codon. Some 3'-untranslated 
      regions (3'-UTRs) are also known to trigger NMD, but the mechanism is less well 
      understood. To further study the role of 3'-UTRs in NMD, a reporter system was 
      designed to examine 3'-UTRs from candidate genes known to produce NMD-sensitive 
      transcripts. Out of eight that were tested, the 3'-UTRs from MSH4 and SPO16 
      caused NMD-dependent mRNA destabilization. Both endogenous genes produce multiple 
      transcripts that differ in length at the 3' end. Detailed studies revealed that 
      the longest of six reporter MSH4-3'-UTR transcripts was NMD-sensitive but five 
      shorter transcripts were insensitive. NMD-dependent degradation of the long 
      transcript required Xrn1, which degrades mRNA from the 5' end. Sensitivity to NMD 
      was not associated with extensive translational read-through past the normal stop 
      codon. To our knowledge, this is the first example where multiple transcripts 
      containing the same ORF are differentially sensitive to NMD in Saccharomyces 
      cerevisiae. The results provide a proof of principle that long 3'-UTRs can 
      trigger NMD, which suggests a potential link between errors in transcription 
      termination or processing and mRNA decay.
FAU - Zaborske, John M
AU  - Zaborske JM
AD  - Laboratory of Genetics and Laboratory of Cell and Molecular Biology, University 
      of Wisconsin, Madison, Wisconsin, United States of America.
FAU - Zeitler, Bethany
AU  - Zeitler B
FAU - Culbertson, Michael R
AU  - Culbertson MR
LA  - eng
GR  - T32 HG002760/HG/NHGRI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20131118
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (3' Untranslated Regions)
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Codon, Nonsense)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (MSH4 protein, S cerevisiae)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (Spo16 protein, S cerevisiae)
RN  - EC 3.1.- (Exoribonucleases)
RN  - EC 3.1.11.- (XRN1 protein, S cerevisiae)
SB  - IM
MH  - *3' Untranslated Regions
MH  - 5' Untranslated Regions
MH  - *Alternative Splicing
MH  - Codon, Nonsense
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - Exons
MH  - Exoribonucleases/genetics/metabolism
MH  - *Gene Expression Regulation, Fungal
MH  - Genes, Reporter
MH  - Introns
MH  - Microtubule-Associated Proteins/genetics/metabolism
MH  - *Nonsense Mediated mRNA Decay
MH  - Open Reading Frames
MH  - Saccharomyces cerevisiae/*genetics/metabolism
MH  - Saccharomyces cerevisiae Proteins/genetics/metabolism
MH  - *Transcription, Genetic
PMC - PMC3832414
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/11/22 06:00
MHDA- 2014/07/01 06:00
PMCR- 2013/11/18
CRDT- 2013/11/22 06:00
PHST- 2013/09/05 00:00 [received]
PHST- 2013/10/17 00:00 [accepted]
PHST- 2013/11/22 06:00 [entrez]
PHST- 2013/11/22 06:00 [pubmed]
PHST- 2014/07/01 06:00 [medline]
PHST- 2013/11/18 00:00 [pmc-release]
AID - PONE-D-13-36648 [pii]
AID - 10.1371/journal.pone.0080981 [doi]
PST - epublish
SO  - PLoS One. 2013 Nov 18;8(11):e80981. doi: 10.1371/journal.pone.0080981. 
      eCollection 2013.