Paralogs hnRNP L and hnRNP LL exhibit overlapping but distinct RNA binding constraints

PLoS One. 2013 Nov 11;8(11):e80701. doi: 10.1371/journal.pone.0080701. eCollection 2013.

Abstract

HnRNP (heterogeneous nuclear ribonucleoprotein) proteins are a large family of RNA-binding proteins that regulate numerous aspects of RNA processing. Interestingly, several paralogous pairs of hnRNPs exist that exhibit similar RNA-binding specificity to one another, yet have non-redundant functional targets in vivo. In this study we systematically investigate the possibility that the paralogs hnRNP L and hnRNP LL have distinct RNA binding determinants that may underlie their lack of functional redundancy. Using a combination of RNAcompete and native gel analysis we find that while both hnRNP L and hnRNP LL preferentially bind sequences that contain repeated CA dinucleotides, these proteins differ in their requirement for the spacing of the CAs. Specifically, hnRNP LL has a more stringent requirement for a two nucleotide space between CA repeats than does hnRNP L, resulting in hnRNP L binding more promiscuously than does hnRNP LL. Importantly, this differential requirement for the spacing of CA dinucleotides explains the previously observed differences in the sensitivity of hnRNP L and LL to mutations within the CD45 gene. We suggest that overlapping but divergent RNA-binding preferences, as we show here for hnRNP L and hnRNP LL, may be commonplace among other hnRNP paralogs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Electrophoretic Mobility Shift Assay
  • Heterogeneous-Nuclear Ribonucleoprotein L / chemistry
  • Heterogeneous-Nuclear Ribonucleoprotein L / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein L / metabolism*
  • Heterogeneous-Nuclear Ribonucleoproteins / chemistry
  • Heterogeneous-Nuclear Ribonucleoproteins / genetics
  • Heterogeneous-Nuclear Ribonucleoproteins / metabolism*
  • Humans
  • RNA Splicing

Substances

  • Heterogeneous-Nuclear Ribonucleoprotein L
  • Heterogeneous-Nuclear Ribonucleoproteins