Full-length transcriptome reconstruction reveals a large diversity of RNA and protein isoforms in rat hippocampus

Nat Commun. 2019 Nov 1;10(1):5009. doi: 10.1038/s41467-019-13037-0.

Abstract

Gene annotation is a critical resource in genomics research. Many computational approaches have been developed to assemble transcriptomes based on high-throughput short-read sequencing, however, only with limited accuracy. Here, we combine next-generation and third-generation sequencing to reconstruct a full-length transcriptome in the rat hippocampus, which is further validated using independent 5´ and 3´-end profiling approaches. In total, we detect 28,268 full-length transcripts (FLTs), covering 6,380 RefSeq genes and 849 unannotated loci. Based on these FLTs, we discover co-occurring alternative RNA processing events. Integrating with polysome profiling and ribosome footprinting data, we predict isoform-specific translational status and reconstruct an open reading frame (ORF)-eome. Notably, a high proportion of the predicted ORFs are validated by mass spectrometry-based proteomics. Moreover, we identify isoforms with subcellular localization pattern in neurons. Collectively, our data advance our knowledge of RNA and protein isoform diversity in the rat brain and provide a rich resource for functional studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Profiling / methods
  • Genomics / methods
  • High-Throughput Nucleotide Sequencing / methods*
  • Hippocampus / metabolism*
  • Molecular Sequence Annotation
  • Open Reading Frames / genetics
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Proteins / genetics*
  • Proteins / metabolism
  • RNA / genetics*
  • RNA / metabolism
  • RNA Isoforms / genetics
  • RNA Isoforms / metabolism
  • Rats, Sprague-Dawley
  • Sequence Analysis, RNA / methods*
  • Transcriptome*

Substances

  • Protein Isoforms
  • Proteins
  • RNA Isoforms
  • RNA