Cyclin L is an RS domain protein involved in pre-mRNA splicing.
We report the cDNA cloning and functional characterization of human cyclin L, a novel cyclin related to the C-type cyclins that are involved in regulation of RNA polymerase II (pol II) transcription. Cyclin L also contains a COOH-terminal dipeptide repeat of alternating arginines and serines, a hallmark of the SR family of splicing factors. We show that recombinant cyclin L interacts with p110 PITSLRE kinase, and that cyclin L antibody co-immunoprecipitates a kinase activity from HeLa nuclear extracts that phosphorylates the carboxyl-terminal domain (CTD) of pol II and splicing factor SC35, and is inhibited by the cdk inhibitor p21. Cyclin L antibody inhibits the second step of RNA splicing in vitro, and recombinant cyclin L protein stimulates splicing under suboptimal conditions. Significantly, the IC(50) for splicing inhibition by p21 is similar to the IC(50) for inhibition of the cyclin L-associated kinase activity. Cyclin L and its associated kinase are thus new members of the pre-mRNA processing machinery.
Dickinson
Liliane A
LA
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Edgar
Alasdair J
AJ
Ehley
Jennifer
J
Gottesfeld
Joel M
JM
D017398:Alternative Splicing / Q000502:physiology*; D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D016213:Cyclins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017931:DNA Primers; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D012322:RNA Precursors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D016213:Cyclins; D017931:DNA Primers; D012322:RNA Precursors; D012333:RNA, Messenger; D011994:Recombinant Proteins