Manuel Ares, Jr.
| Distinguished Professor of MCD Biology B. S., Cornell University Ph.D., University of California, San Diego Postdoctorate, Yale University School of Medicine |
Intron Removal, Alternative Splicing, and Genomics
Our work centers on the mechanisms and regulation of splicing. Splicing is required to remove intron sequences from pre-mRNA and create coding sequences for translation. We try to understand:
(1) the mechanism of action of the core components of the spliceosome, in particular the snRNAs and their rearrangements during assembly of the spliceosome and catalysis of the splicing reactions,
(2) the regulation of alternative splicing at a mechanistic level including the coupling of splicing to transcription and RNA decay mechanisms, and
(3) the coordinate regulation of splicing events in developing systems.
Please follow this link to find the lab's publications in the National Library of Medicine's PubMed database.
Model for a proposed role for ultraconserved elements in maintaining homeostasis of splicing factor activities in mammalian genomes. Positively acting splicing factors promote inclusion of special stop codon-containing alternative exons in their own pre-mRNA, thus down regulating themselves through nonsense-mediated decay when they accumulate to excess. Conversely, negatively acting splicing factors repress the inclusion of a coding exon that is not a mulitple of three, creating out of frame mRNA that also results in downregulation through NMD. The result of these autoregulatory controls on splicing factor expression help maintain a stable balance of the antagonistic splicing factor activties that lead to proper inclusion of all exons. For more details, see Ni et al. 2007, Genes & Development 21: 707-718.
