HP1γ binding pre‐mRNA intronic repeats modulates RNA splicing decisions

Christophe Rachez (1, 2, 3) , Rachel Legendre (4, 5) , Mickaël Costallat (3, 1, 2) , Hugo Varet (4, 5) , Jia Yi (1, 6) , Etienne Kornobis (1) , Christian Muchardt (3, 1, 2)

1 Régulation épigénétique - Epigenetic regulation
2 IBPS - Institut de Biologie Paris Seine
3 B2A - Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing
4 C2RT - Pôle Biomics
5 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB
6 ED515 - Ecole Doctorale Complexité du Vivant

HP1 proteins are best known as markers of heterochromatin and gene silencing. Yet, they are also RNA-binding proteins and the HP1c/CBX3 family member is present on transcribed genes together with RNA polymerase II, where it regulates cotranscriptional processes such as alternative splicing. To gain insight in the role of the RNA-binding activity of HP1c in transcriptionally active chromatin, we have captured and analysed RNAs associated with this protein. We find that HP1c is specifically targeted to hexameric RNA motifs and coincidentally transposable elements of the SINE family. As these elements are abundant in introns, while essentially absent from exons, the HP1c RNA association tethers unspliced pre-mRNA to chromatin via the intronic regions and limits the usage of intronic cryptic splice sites. Thus, our data unveil novel determinants in the relationship between chromatin and co-transcriptional splicing.

Keywords: Cbx3; chromatin; HP1; RNA; splicing Subject Categories Chromatin; Transcription & Genomics; RNA Biology; splicing

Domains: Life Sciences [q-bio]

Christophe Rachez, Rachel Legendre, Mickaël Costallat, Hugo Varet, Jia Yi, et al.. HP1γ binding pre‐mRNA intronic repeats modulates RNA splicing decisions. EMBO Reports, 2021, pp.e52320. ⟨10.15252/embr.202052320⟩. ⟨pasteur-03303092⟩