Whole transcriptome sequencing of the aging rat brain reveals dynamic RNA changes in the dark matter of the genome.

Age
Shona H WoodJoão Pedro de Magalhães

Abstract

Brain aging frequently underlies cognitive decline and is a major risk factor for neurodegenerative conditions. The exact molecular mechanisms underlying brain aging, however, remain unknown. Whole transcriptome sequencing provides unparalleled depth and sensitivity in gene expression profiling. It also allows non-coding RNA and splice variant detection/comparison across phenotypes. Using RNA-seq to sequence the cerebral cortex transcriptome in 6-, 12- and 28-month-old rats, age-related changes were studied. Protein-coding genes related to MHC II presentation and serotonin biosynthesis were differentially expressed (DE) in aging. Relative to protein-coding genes, more non-coding genes were DE over the three age-groups. RNA-seq quantifies not only levels of whole genes but also of their individual transcripts. Over the three age-groups, 136 transcripts were DE, 37 of which were so-called dark matter transcripts that do not map to known exons. Fourteen of these transcripts were identified as novel putative long non-coding RNAs. Evidence of isoform switching and changes in usage were found. Promoter and coding sequence usage were also altered, hinting of possible changes to mitochondrial transport within neurons. Therefore, in add...Continue Reading

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Citations

Oct 27, 2012·Biogerontology·Sara FidalgoShona H Wood
May 28, 2013·Biogerontology·Andrew P HolmesJoão Pedro de Magalhães
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Datasets Mentioned

BETA
GSE34272

Methods Mentioned

BETA
RNA-Seq
dissection
PCR

Software Mentioned

BLAST
Galaxy
EdgeR
Python
cufflinks
DAVID
EMBOSS
Ensembl
RFAM
Tophat

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