Heteromeric RNP Assembly at LINEs Controls Lineage-Specific RNA Processing.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30078707.
- Also identified by DOI 10.1016/j.cell.2018.07.001 and PMC identifier 6108849.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Long mammalian introns make it challenging for the RNA processing machinery to identify exons accurately. We find that LINE-derived sequences (LINEs) contribute to this selection by recruiting dozens of RNA-binding proteins (RBPs) to introns. This includes MATR3, which promotes binding of PTBP1 to multivalent binding sites within LINEs. Both RBPs repress splicing and 3' end processing within and around LINEs. Notably, repressive RBPs preferentially bind to evolutionarily young LINEs, which are located far from exons. These RBPs insulate the LINEs and the surrounding intronic regions from RNA processing. Upon evolutionary divergence, changes in RNA motifs within LINEs lead to gradual loss of their insulation. Hence, older LINEs are located closer to exons, are a common source of tissue-specific exons, and increasingly bind to RBPs that enhance RNA processing. Thus, LINEs are hubs for the assembly of repressive RBPs and also contribute to the evolution of new, lineage-specific transcripts in mammals. VIDEO ABSTRACT.
Medical subject headings
- Heterogeneous-Nuclear Ribonucleoproteins
- Long Interspersed Nucleotide Elements
- Nuclear Matrix-Associated Proteins
- Polyadenylation
- Polypyrimidine Tract-Binding Protein
- RNA
- RNA-Binding Proteins