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

• Project/Area Number: 16580073
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied biochemistry
• Research Institution: Kyoto University
• Principal Investigator: MASUDA Seiji Kyoto University, Graduate School of Biostudies, Associate professor, 生命科学研究科, 助教授 (20260614)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000); Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: transcription elongation / mRNA export / splicing / mRNA / 転写 / 核外輸送

Research Abstract

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.

Research Products

• [Journal Article] Recruitment of the human TREX complex to mRNA during splicing (2005)
  • Author(s): Masuda, S., Das, R., Cheng, H., Hurt, E., Dorman, N., Reed,R.
  • Journal Title: Genes & Development 19 Pages: 1512-1517
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Recruitment of human TREX complex to mRNA during splicing. (2005)
  • Author(s): Masuda, S., Das, R., Cheng, H., Hurt, E., Dorman, N., Reed, R.
  • Journal Title: Genes and Development 19 Pages: 1512-1517
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Recruitment of the human TREX complex to mRNA during splicing (2005)
  • Author(s): Masuda, S., Das, R., Cheng, H., Hurt, E., Dorman, N., Reed, R.
  • Journal Title: Genes & Development 19 Pages: 1512-1517