SCNM1, a putative RNA splicing factor that modifies disease severity in mice

SCNM1, a putative RNA splicing factor that modifies disease severity in mice.

Science (New York, N.Y.), Vol. 301, No. 5635. (15 August 2003), pp. 967-969, doi:10.1126/science.1086187

by David A. Buchner, Michelle Trudeau, Miriam H. Meisler

I use this paper in my graduate genetics course.  It describes the use of inbred strains to map and molecularly identify genes and illustrates a case of strain-specific phenotypes and genetic interactions.  It simultaneously illustrates the power of working with inbred strains and the caveat that phentypes can be strain-specific.

All 4096 hexamers evaluated as exonic splicing elements

Exon sequences have a large effect on splicing efficiency. Specific sequences can act as ESEs (exonic splicing enhancers) to promote splicing, or as ESSs (exonic splicing suppressors) to reduce splicing. In the August 2011 issue of Genome Research, Ke et al. describe a comprehensive quantitative measure of the splicing impact of all 4,096 6-mer sequences using an Illumina Genome Analyzer to compare spliced transcripts with an input library. They tested five positions within two different internal exons in a minigene system and sequenced millions of successfully spliced transcripts after transfection of human cells. Specific hexamers had different effects in different positions, but these were correlated, and the effect on splicing of each 6-mer could be quantified. Many complications (secondary structure, synergy, effect on chromatin) are addressed by this study, which provides a huge data set. However, this is just the beginning. This paper examines only a single cell type, and it concerns only a single type of alternative splicing - exon inclusion. This high throughput approach, which captures the power of high throughput sequencing, will certainly be extended to other contexts in alternative splicing, and may prove useful for defining other nucleic acid regulatory motifs.