Yizhe Zhang / Shanghai Institute of Biological Sciences, Chinese Academy of Sciences
Chunxiang Chen / Shanghai Institute of Biological Sciences, Chinese Academy of Sciences
Jian-Kang Zhu / Shanghai Institute of Biological Sciences, Chinese Academy of Sciences
Cheng-Guo Duan / Shanghai Institute of Biological Sciences, Chinese Academy of Sciences
In eukaryotes, heterochromatins featured by high density of DNA methylation and repressive histone modifications are present not only in intergenic transposable elements (TEs) but also in protein-coding genes. In most cases, intergenic heterochromatin exerts deleterious effects on the expression of downstream genes. While, it is unclear about the biological function of intragenic heterochromatin. Recently, we revealed that ASI1-AIPP1-EDM2 (AAE complex) controls the RNA processing of intronic TE-containing genes. AAE complex target genes are involved in multiple biological process, including development and disease resistance. In AAE complex, ASI1 is an RNA-binding protein capable of binding to the pre-mRNA specifically at the heterochromatic regions. EDM2 recognizes H3K9me2 and other histone modifications via its PHD fingers. AIPP3 mediates the association of ASI1 and EDM2 in vivo. We revealed that ASI1 and EDM2 target common genomic regions, and both ASI1 and EDM2 prefer to bind gene-TE overlap regions, especially in the intronic TE-containing genes. PolyA-specific sequencing proved that AAE complex promotes the usage of distal polyA sites. We further revealed that an RNA binding protein attenuates AAE complex by promoting proximal polyadenylation, suggesting a bidirectional regulation of intragenic heterochromatin-dependent RNA polyadenylation. Our findings advance our understanding of the interplay between epigenetic modifications and RNA processing in eukaryotes.