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Carnegie Mellon University research reveals how cells process large genes

er insect species.

"Our experimental results agreed with the computational findings, indicating that these ratchetting points mediate the removal of intron subfragments in one direction as the gene is transcribed initially from DNA into RNA," Lopez said.

Lopez found that predicted recursive splice sites were 10 times more likely than expected to be found in introns greater than 200 kilobases in length, and 92 percent of them were conserved over at least 25 million years of insect evolution. This discovery strongly suggests that recursive splicing plays a special role in the correct expression of large genes. Bioinformatic and phylogenetic analyses conducted by Lopez also indicate that recursive splicing plays a role in at least 124 fruitfly introns, with up to seven potential cutting steps identified for a single intron. Similar analyses suggest that the same process also occurs in large introns of mammals, including humans, and the Lopez team is now testing this hypothesis experimentally.

"The striking evolutionary conservation of ratchetting points suggests that recursive splicing provides specific advantages for large introns," Lopez said. "One possibility is that recursive splicing prevents the generation of long RNA transcripts that could form structures that interfere with correct processing into mRNA. Another is that recursive splicing might help stimulate transcription through long introns by promoting interactions between the splicing and transcription machineries. We also know already that recursive splicing is used to control the removal of certain exons from mRNAs, generating structural and functional variation among the gene products."


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Source:Carnegie Mellon University


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