|Title||Global analysis of the nuclear processing of transcripts with unspliced U12-type introns by the exosome|
|Author(s)||Niemelä, Elina H.; Oghabian, Ali; Staals, Raymond H.J.; Greco, Dario; Pruijn, Ger J.M.; Frilander, Mikko J.|
|Source||Nucleic acids research 42 (2014)11. - ISSN 0305-1048 - p. 7358 - 7369.|
|Publication type||Refereed Article in a scientific journal|
U12-type introns are a rare class of introns in the genomes of diverse eukaryotes. In the human genome, they number over 700. A subset of these introns has been shown to be spliced at a slower rate compared to the major U2-type introns. This suggests a rate-limiting regulatory function for the minor spliceosome in the processing of transcripts containing U12-type introns. However, both the generality of slower splicing and the subsequent fate of partially processed pre-mRNAs remained unknown. Here, we present a global analysis of the nuclear retention of transcripts containing U12-type introns and provide evidence for the nuclear decay of such transcripts in human cells. Using SOLiD RNA sequencing technology, we find that, in normal cells, U12-type introns are on average 2-fold more retained than the surrounding U2-type introns. Furthermore, we find that knockdown of RRP41 and DIS3 subunits of the exosome stabilizes an overlapping set of U12-type introns. RRP41 knockdown leads to slower decay kinetics of U12-type introns and globally upregulates the retention of U12-type, but not U2-type, introns. Our results indicate that U12-type introns are spliced less efficiently and are targeted by the exosome. These characteristics support their role in the regulation of cellular mRNA levels.