PMID- 23151878
OWN - NLM
STAT- MEDLINE
DCOM- 20130221
LR  - 20211021
IS  - 1469-9001 (Electronic)
IS  - 1355-8382 (Print)
IS  - 1355-8382 (Linking)
VI  - 19
IP  - 1
DP  - 2013 Jan
TI  - Cleavage and polyadenylation specificity factor 1 (CPSF1) regulates alternative 
      splicing of interleukin 7 receptor (IL7R) exon 6.
PG  - 103-15
LID - 10.1261/rna.035410.112 [doi]
AB  - Interleukin 7 receptor, IL7R, is expressed exclusively on cells of the lymphoid 
      lineage, and its expression is crucial for the development and maintenance of T 
      cells. Alternative splicing of IL7R exon 6 results in membrane-bound (exon 6 
      included) and soluble (exon 6 skipped) IL7R isoforms. Interestingly, the 
      inclusion of exon 6 is affected by a single-nucleotide polymorphism associated 
      with the risk of developing multiple sclerosis. Given the potential association 
      of exon 6 inclusion with multiple sclerosis, we investigated the cis-acting 
      elements and trans-acting factors that regulate exon 6 splicing. We identified 
      multiple exonic and intronic cis-acting elements that impact inclusion of exon 6. 
      Moreover, we utilized RNA affinity chromatography followed by mass spectrometry 
      to identify trans-acting protein factors that bind exon 6 and regulate its 
      splicing. These experiments identified cleavage and polyadenylation specificity 
      factor 1 (CPSF1) among protein-binding candidates. A consensus polyadenylation 
      signal AAUAAA is present in intron 6 of IL7R directly downstream from the 5' 
      splice site. Mutations to this site and CPSF1 knockdown both resulted in an 
      increase in exon 6 inclusion. We found no evidence that this site is used to 
      produce cleaved and polyadenylated mRNAs, suggesting that CPSF1 interaction with 
      intronic IL7R pre-mRNA interferes with spliceosome binding to the exon 6 5' 
      splice site. Our results suggest that competing mRNA splicing and polyadenylation 
      regulate exon 6 inclusion and consequently determine the ratios of soluble to 
      membrane-bound IL7R. This may be relevant for both T cell ontogeny and function 
      and development of multiple sclerosis.
FAU - Evsyukova, Irina
AU  - Evsyukova I
AD  - Department of Biochemistry, Duke University Medical Center, Durham, North 
      Carolina 27710, USA.
FAU - Bradrick, Shelton S
AU  - Bradrick SS
FAU - Gregory, Simon G
AU  - Gregory SG
FAU - Garcia-Blanco, Mariano A
AU  - Garcia-Blanco MA
LA  - eng
GR  - R01 NS060925/NS/NINDS NIH HHS/United States
GR  - 5R01-NS060925/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20121114
PL  - United States
TA  - RNA
JT  - RNA (New York, N.Y.)
JID - 9509184
RN  - 0 (Cleavage And Polyadenylation Specificity Factor)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA Splice Sites)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Interleukin-7)
RN  - 0 (Trans-Activators)
SB  - IM
MH  - *Alternative Splicing
MH  - Animals
MH  - Cell Line
MH  - Chromatography, Affinity/methods
MH  - Cleavage And Polyadenylation Specificity Factor/genetics/*metabolism
MH  - Exons/*genetics
MH  - Gene Silencing
MH  - Humans
MH  - Introns
MH  - Mass Spectrometry
MH  - Multiple Sclerosis/genetics/metabolism
MH  - Mutation
MH  - Polymorphism, Single Nucleotide
MH  - Protein Isoforms/biosynthesis
MH  - RNA Splice Sites
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Receptors, Interleukin-7/*genetics
MH  - Spliceosomes/metabolism
MH  - Trans-Activators/metabolism
PMC - PMC3527722
EDAT- 2012/11/16 06:00
MHDA- 2013/02/22 06:00
PMCR- 2013/01/01
CRDT- 2012/11/16 06:00
PHST- 2012/11/16 06:00 [entrez]
PHST- 2012/11/16 06:00 [pubmed]
PHST- 2013/02/22 06:00 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - rna.035410.112 [pii]
AID - RA [pii]
AID - 10.1261/rna.035410.112 [doi]
PST - ppublish
SO  - RNA. 2013 Jan;19(1):103-15. doi: 10.1261/rna.035410.112. Epub 2012 Nov 14.