Evidence for the regulation of alternative splicing via complementary DNA sequence repeats.
BACKGROUND
While the mechanism for regulating alternative splicing is poorly understood, secondary structure has been shown to be integral to this process. Due to their propensity for forming complementary hairpin loops and their elevated mutation rates, tandem repeated sequences have the potential to influence splicing regulation.


RESULTS
An analysis of human intronic sequences reveals a strong correlation between alternative splicing and the prevalence of mono- through hexanucleotide tandem repeats that may engage in complementary pairing in introns that flank alternatively spliced exons. While only 44% of the 18 173 genes in the Human Alternative Splicing Database are known to be alternatively spliced, they contain 84% of the 694 237 intronic complementary repeat pairs. Significantly, the normalized frequency and distribution of repeat sequences, independent of their potential for pairing, are indistinguishable between alternatively spliced and non-alternatively spliced genes. Thus, the increased prevalence of repeats with pairing potential in alternatively spliced genes is not merely a consequence of more repeats or repeat composition bias. These results suggest that complementary repeats may play a role in the regulation of alternative splicing.


BACKGROUND
harold.garner@utsouthwestern.edu.
Lian
Yun
Y
Department of Biochemistry, McDermott Center for Human Growth and Development and Center for Biomedical Inventions, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Garner
Harold R
HR
D017398:Alternative Splicing / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods*; D018076:DNA, Complementary / Q000235:genetics*; D019317:Evidence-Based Medicine / Q000379:methods; D005786:Gene Expression Regulation / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D008957:Models, Genetic; D015233:Models, Statistical; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D016415:Sequence Alignment / Q000379:methods; D017422:Sequence Analysis, DNA / Q000379:methods*
D018076:DNA, Complementary