Staying on message: ensuring fidelity in pre-mRNA splicing
The faithful expression of genes requires that cellular machinery select substrates with high specificity at each step in gene expression. High specificity is particularly important at the stage of nuclear pre-mRNA splicing, during which the spliceosome selects splice sites and excises intervening introns. With low specificity, the usage of alternative sites would yield insertions, deletions and frame shifts in mRNA. Recently, biochemical, genetic and genome-wide approaches have significantly advanced our understanding of splicing fidelity. In particular, we have learned that DExD/H-box ATPases play a general role in rejecting and discarding suboptimal substrates and that these factors serve as a paradigm for proofreading NTPases in other systems. Recent advances have also defined fundamental questions for future investigations.
Additional Information© 2012 Elsevier. Available online 5 May 2012. As a result of space constraints, we were unfortunately unable to highlight all relevant stories. We apologize to those whose work was not discussed or cited. We thank P. Koodathingal, D. Qin, A. Wlodaver, Y. Zeng, K. Nielsen and C. Query for comments on the manuscript. Research in our laboratory into splicing fidelity has been funded by the National Institutes of Health (NIH) (GM062264). D.R.S. was partially supported by National Institutes of Health Grant T32 GM007197.
Accepted Version - nihms-375557.pdf