Computational Analysis of an Evolutionarily Conserved VertebrateMuscle Alternative Splicing Program

Journal Article · Thu Jun 15 04:00:00 EDT 2006 · Nucleic Acids Research

OSTI ID:923004

Das, Debopriya; Clark, Tyson A; Schweitzer, Anthony; Marr, Henry; Yamamoto, Miki L; Parra, Marilyn K; Arribere, Josh; Minovitsky, Simon; Dubchak, Inna; Blume, John E; Conboy, John G

A novel exon microarray format that probes gene expression with single exon resolution was employed to elucidate critical features of a vertebrate muscle alternative splicing program. A dataset of 56 microarray-defined, muscle-enriched exons and their flanking introns were examined computationally in order to investigate coordination of the muscle splicing program. Candidate intron regulatory motifs were required to meet several stringent criteria: significant over-representation near muscle-enriched exons, correlation with muscle expression, and phylogenetic conservation among genomes of several vertebrate orders. Three classes of regulatory motifs were identified in the proximal downstream intron, within 200nt of the target exons: UGCAUG, a specific binding site for Fox-1 related splicing factors; ACUAAC, a novel branchpoint-like element; and UG-/UGC-rich elements characteristic of binding sites for CELF splicing factors. UGCAUG was remarkably enriched, being present in nearly one-half of all cases. These studies suggest that Fox and CELF splicing factors play a major role in enforcing the muscle-specific alternative splicing program, facilitating expression of a set of unique isoforms of cytoskeletal proteins that are critical to muscle cell differentiation. Supplementary materials: There are four supplementary tables and one supplementary figure. The tables provide additional detailed information concerning the muscle-enriched datasets, and about over-represented oligonucleotide sequences in the flanking introns. The supplementary figure shows RT-PCR data confirming the muscle-enriched expression of exons predicted from the microarray analysis.

• Research Organization: Ernest Orlando Lawrence Berkeley NationalLaboratory, Berkeley, CA (US)
• Sponsoring Organization: USDOE Director, Office of Science. Office of Biological andEnvironmental Research. Life Sciences Division
• DOE Contract Number: AC02-05CH11231
• OSTI ID: 923004
• Report Number(s): LBNL--60642; BnR: 400412000
• Journal Information: Nucleic Acids Research, Journal Name: Nucleic Acids Research Vol. 35; ISSN 0305-1048; ISSN NARHAD
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CELL DIFFERENTIATION
EXONS
GENES
INTRONS
MUSCLES
OLIGONUCLEOTIDES
PROBES
PROTEINS
RESOLUTION
SPLICING
TARGETS
VERTEBRATES