Image

Alain Laederach - University of North Carolina, Chapel Hill

Host: Phil Bevilacqua

"Pre-mRNA ensemble structures and their role in alternative splicing"

Abstract: Introns, especially in the human genome, makeup the vast majority of a gene in terms of nucleotides transcribed. Although they are eventually spliced out of the mature message, their median length of over 1600 nucleotides means a large number of these RNAs exist on minute timescales, suggesting they have time to fold into complex structures. Our lab has leveraged mutational profiling technologies coupled with advanced thermodynamic folding algorithms to study intron structures in cells. These techniques confirm important structures fold, and furthermore these structures regulate splicing. We have also shown that disease causing variants affect structures in introns and cause disease. Furthermore, repetitive elements (retrotransposons) are ubiquitous in intron sequences, and we will show that the structures of these elements play an important role, especially in back splicing. In effect, we are beginning to reveal RNA structure as a third and under appreciated component of the splicing code.