P.475 - Alternative splicing in titin: new insights into exon usage

Abstract

TTN gene contains 364 exons and encodes titin, a giant protein with multiple functions in skeletal and cardiac muscles. As a result of alternative splicing, several titin isoforms are expressed. TTN isoforms can be divided into three main classes based on the presence of the N2A and N2B elements in the I-band region. N2A isoforms, characterized by the inclusion of the N2A element and exclusion of the cardiac-specific N2B element, are expressed in the skeletal muscles. N2B (N2B element only) and N2BA (including both the N2B and N2A elements) isoforms are expressed in the heart. Further variability is seen within each class as a consequence of a variable exon usage in different muscles and across developmental and physiological states. With over 1 million potential splicing variants, TTN could be the most alternatively spliced human gene. Expression data obtained from microarray, RNA-seq and RT-PCRs reveals new insights into the TTN exon usage. A better understanding of TTN alternative transcripts, their biological meaning and their specific tissue expression is crucial for the clinical interpretation of molecular findings.