Minimal Functional Domains of Paralogues hnRNP L and hnRNP LL Exhibit Mechanistic Differences in Exonic Splicing Repression

In this study, we use an MS2-tethering assay to delineate the minimal domains of hnRNP L and hnRNP LL which are required for repressing exon inclusion. We demonstrate that for both proteins, regions outside the RRMs – the N-terminal region, and a linker sequence between RRMs 2 and 3 – are necessary for exon repression, but are only sufficient for repression in the case of hnRNP LL. In addition, both proteins require at least one RRM for maximal repression. Notably, we demonstrate that the region encompassing RRMs 1-2 of hnRNP LL imparts a second silencing activity not observed for hnRNP L. This additional functional component of hnRNP LL is consistent with the fact that the full length hnRNP LL has greater silencing activity than hnRNP L. Thus, our data provide important insight into the functional and mechanistic variations that can exist between two highly related hnRNP proteins.

Source: BJ Gene - May 7, 2013 Category: Biochemistry Authors: G Shankarling, K W Lynch Tags: BJ Gene Source Type: research