RBFOX and PTBP1 proteins regulate the alternative splicing of micro-exons in human brain transcripts

Yang I Li, Luis Sanchez-Pulido, Wilfried Haerty, Chris P Ponting

Research output: Contribution to journalArticlepeer-review

Abstract

Ninety-four percent of mammalian protein-coding exons exceed 51 nucleotides (nt) in length. The paucity of micro-exons (≤ 51 nt) suggests that their recognition and correct processing by the splicing machinery present greater challenges than for longer exons. Yet, because thousands of human genes harbor processed micro-exons, specialized mechanisms may be in place to promote their splicing. Here, we survey deep genomic data sets to define 13,085 micro-exons and to study their splicing mechanisms and molecular functions. More than 60% of annotated human micro-exons exhibit a high level of sequence conservation, an indicator of functionality. While most human micro-exons require splicing-enhancing genomic features to be processed, the splicing of hundreds of micro-exons is enhanced by the adjacent binding of splice factors in the introns of pre-messenger RNAs. Notably, splicing of a significant number of micro-exons was found to be facilitated by the binding of RBFOX proteins, which promote their inclusion in the brain, muscle, and heart. Our analyses suggest that accurate regulation of micro-exon inclusion by RBFOX proteins and PTBP1 plays an important role in the maintenance of tissue-specific protein–protein interactions.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalGenome Research
Volume25
Issue number1
Early online date18 Dec 2014
DOIs
Publication statusPublished - Jan 2015

Keywords

  • Alternative Splicing
  • Animals
  • Brain
  • Chromosome Mapping
  • Conserved Sequence
  • Exons
  • Gene Expression Regulation
  • Genomics
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Humans
  • Introns
  • Mice
  • Nucleotides
  • Polypyrimidine Tract-Binding Protein
  • Protein Interaction Domains and Motifs
  • RNA, Messenger
  • RNA-Binding Proteins

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