Institut de Biologie Paris-Seine, Sorbonne Université, Paris, France.
CNRS UMR 8256, Biological Adaptation and Aging, Paris, France.
EMBO Rep. 2021 Sep 6;22(9):e52320. doi: 10.15252/embr.202052320. Epub 2021 Jul 27.
HP1 proteins are best known as markers of heterochromatin and gene silencing. Yet, they are also RNA-binding proteins and the HP1γ/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 HP1γ in transcriptionally active chromatin, we have captured and analysed RNAs associated with this protein. We find that HP1γ 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 HP1γ 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.
HP1 蛋白作为异染色质和基因沉默的标志物而广为人知。然而，它们也是 RNA 结合蛋白，HP1γ/CBX3 家族成员与 RNA 聚合酶 II 一起存在于转录基因上，在那里它调节共转录过程，如选择性剪接。为了深入了解 HP1γ 在转录活性染色质中的 RNA 结合活性的作用，我们已经捕获和分析了与这种蛋白质相关的 RNA。我们发现 HP1γ 特异性地靶向六聚体 RNA 基序和顺式作用元件家族的 SINE。由于这些元件在 introns 中丰富，而在 exons 中基本不存在，因此 HP1γ RNA 结合将未剪接的前体 mRNA 通过内含子区域与染色质连接，并限制内含子隐匿剪接位点的使用。因此，我们的数据揭示了染色质和共转录剪接之间关系的新决定因素。
