Biochemical and structural analysis of human THO complex that regulates the mRNA synthesis and maturation

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mRNA, used as a template for protein synthesis in eukaryotes, is synthesized by RNA polymerase II complex in nucleus and undergoes a multiple process for maturation including capping, splicing and poly-adenylation. Recent lines of evidence indicate that these mRNA maturation process form a extensive network by a number of coupling factors. We found THO complex as a one of these coupling factor. Furthermore, we named the TREX complex as transcription and export coupling complex by combined with THO complex, Sub2 (UAP56 in human) and Yra1 (Aly in human), first one is mainly supposed to act as a transcription elongation and middle and last ones act as export factors. Previous studies indicate that THO complex in yeast directly recruited into transcribing RNA polymerase II elongation complex and THO complex, in turn, recruits Sub2 and Yra1, and thereby couples transcription and export. In this study, we have investigated the characterization and functional analysis of human THO complex. We found, first, human THO complex is composed of six protein components, second, does not affect the mRNA transcription and splicing in contrast to yeast case, and third, is recruited on mRNA during splicing. We, therefore, hypothesized that THO complex recruitment onto mRNA is regulated by the intron in general. This idea is also supported by the finding that intron in yeast gene inhibits the recruitment of THO complex to transcribing pre-mRNA.