hLodestar/HuF2 interacts with CDC5L and is involved in pre-mRNA splicing.
hLodestar/HuF2 belongs to the SNF2 family of proteins. This family of proteins has been shown to play a critical role in altering protein-DNA interactions in a variety of cellular contexts. We have identified an unexpected interaction between hLodestar/HuF2 and CDC5L in both the yeast two-hybrid system and HeLa nuclear extract. CDC5L is a well-characterized pre-mRNA splicing factor in yeast and humans. Our findings demonstrate that hLodestar/HuF2 associates with human splicing complexes. We also found that a truncated hLodestar/HuF2 polypeptide that overlaps with the CDC5L-binding region can inhibit pre-mRNA splicing by disrupting spliceosome assembly. These findings indicate that hLodestar/HuF2 may have a role in pre-mRNA splicing. These data are consistent with a close co-ordination of the transcription and splicing pathways in eukaryotes. Although many members of the DExH/D helicase superfamily have been linked to pre-mRNA splicing, this is the first SNF2 family member to be implicated in this pathway.
Leonard
Deana
D
Department of Molecular Genetics, M.D. Anderson Cancer Center, The University of Texas, Houston, TX 77030, USA.
Ajuh
Paul
P
Lamond
Angus I
AI
Legerski
Randy J
RJ
D000251:Adenosine Triphosphatases; D017398:Alternative Splicing; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D004591:Electrophoresis, Polyacrylamide Gel; D006367:HeLa Cells; D006801:Humans; D013058:Mass Spectrometry; D008957:Models, Genetic; D011233:Precipitin Tests; D011485:Protein Binding; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C071248:lds protein, Drosophila; D004247:DNA; D000251:Adenosine Triphosphatases; C477874:TTF2 protein, human