Promoter choice determines splice site selection in protocadherin alpha and gamma pre-mRNA splicing.
A family of mammalian protocadherin (Pcdh) proteins is encoded by three closely linked gene clusters (alpha, beta, and gamma). Multiple alpha and gamma Pcdh mRNAs are expressed in distinct patterns in the nervous system and are generated by alternative pre-mRNA splicing between different "variable" exons and three "constant" exons within each cluster. We show that each Pcdh variable exon is preceded by a promoter and that promoter choice determines which variable exon is included in a Pcdh mRNA. In addition, we provide evidence that alternative splicing of variable exons within a gene cluster occurs via a cis-splicing mechanism. However, virtually every variable exon can engage in trans-splicing with constant exons from another cluster, albeit at a far lower level.
Tasic
Bosiljka
B
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Nabholz
Christoph E
CE
Baldwin
Kristin K
KK
Kim
Youngwook
Y
Rueckert
Erroll H
EH
Ribich
Scott A
SA
Cramer
Paula
P
Wu
Qiang
Q
Axel
Richard
R
Maniatis
Tom
T
D000483:Alleles; D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D015820:Cadherins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020040:Trans-Splicing / Q000235:genetics; D014158:Transcription, Genetic
D015820:Cadherins; D020033:Protein Isoforms; D011498:Protein Precursors; D012322:RNA Precursors; D012333:RNA, Messenger