An impact of HP1γ on the fidelity of pre-mRNA splicing arises from its ability to bind RNA via intronic repeated sequences.
Rachez, C.; Legendre, R.; Costallat, M.; Varet, H.; Yi, J.; Kornobis, E.; Proux, C.; Muchardt, C.
Show abstract
HP1 proteins are best known as markers of heterochromatin and gene silencing. Yet, they are also RNA-binding proteins and the HP1{gamma}/Cbx3 family member is present on transcribed genes together with RNA polymerase II, where it regulates co-transcriptional processes such as alternative splicing. To gain insight in the role of the RNA binding activity of HP1{gamma} in transcriptionally active chromatin, we have captured and analyzed RNAs associated with this protein. We find that HP1{gamma} specifically recognizes hexameric RNA motifs and coincidentally transposable elements of the SINE family. As these elements are abundant in introns, while essentially absent from exons, the HP1{gamma} RNA binding activity tethers unspliced pre-mRNA to chromatin via the intronic region and limits the usage of intronic cryptic splice sites. Thus, our data unveil novel determinants in the relationship between chromatin and co-transcriptional splicing.
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