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The yeast THO complex forms a 5-subunit assembly that directly interacts with active chromatin.

Gewartowski K, Cuéllar J, Dziembowski A, Valpuesta JM - Bioarchitecture (2012)

Bottom Line: Recent data indicates that the THO complex is necessary for the proper expression of some genes, assurance of genetic stability by preventing transcription-associated recombination.We discuss the consequences of THO interaction with nucleic acids through the unfolded C-terminal region of Tho2, highlighting the importance of unfolded regions in eukaryotic proteins.Finally, we comment on THO recruitment to active chromatin, a role that is linked to mRNA biogenesis.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biochemistry and Biophysics; Polish Academy of Sciences; Warsaw, Poland; Department of Genetics and Biotechnology; Faculty of Biology; University of Warsaw; Warsaw, Poland.

ABSTRACT
The THO complex is a nuclear structure whose architecture is conserved among all kingdoms and plays an important role in mRNP biogenesis connecting transcription elongation with mRNA maturation and export. Recent data indicates that the THO complex is necessary for the proper expression of some genes, assurance of genetic stability by preventing transcription-associated recombination. Yeast THO has been described as a heterotetramer (Tho2, Hpr1, Mft1 and Thp2) that performs several functions through the interaction with other proteins like Tex1 or the mRNA export factors Sub2 and Yra1, with which it forms the TRanscription and EXport complex (TREX). In this article we review the cellular role of THO, which we show to be composed of five subunits with Tex1 being also an integral part of the complex. We also show a low-resolution structure of THO and localize some of its components. We discuss the consequences of THO interaction with nucleic acids through the unfolded C-terminal region of Tho2, highlighting the importance of unfolded regions in eukaryotic proteins. Finally, we comment on THO recruitment to active chromatin, a role that is linked to mRNA biogenesis.

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Figure 1. The THO complex couples RNA transcription elongation, mRNP formation and export. The THO binds active chromatin promoting association of Sub2 and Yra1 with the mRNP particle what facilitates mRNP export and prevents RNA/DNA hybrid formation (R-loops).
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Figure 1: Figure 1. The THO complex couples RNA transcription elongation, mRNP formation and export. The THO binds active chromatin promoting association of Sub2 and Yra1 with the mRNP particle what facilitates mRNP export and prevents RNA/DNA hybrid formation (R-loops).

Mentions: Transcription of pre-mRNA, its maturation and mRNA export to the cytoplasm are a chain of processes involving cooperation of many proteins and assemblies. Over the years these processes have been intensively, albeit independently investigated. However, the acquired knowledge has led to a new vision of these processes as working in a coordinated manner. One of the examples of the connection between all the steps involved in RNA biogenesis is the role of the THO complex, thought to be formed by Tho2 (180 kDa), Hpr1 (90 kDa), Mft1 (45 kDa), and Thp2 (30 kDa) proteins.1 During transcription elongation, the THO complex is involved in packing pre-mRNA molecules into RNA–protein assemblies termed mRNPs2 and is also essential for efficient co-transcriptional recruitment of mRNA export factors Yra1 and Sub23 (Fig. 1). Disruption of any of these tightly coupled steps of production of translation-competent mRNA in the cytoplasm leads to the activation of the RNA surveillance pathway and to the subsequent degradation of non-active mRNA molecules.4 Lack of any of the THO subunits in yeast results in several molecular phenotypes like impairment of mRNP formation, that in turn leads to defects in transcription elongation and export. Lack of the Hpr1 subunit causes mRNA to remain trapped in the transcription sites giving rise to RNA/DNA hybrids (R-loops), which causes hyperrecombination and genomic instability.5 Deletion of the Mtf1 subunit promotes the accumulation of transcribed but not matured and exported RNA, which, together with transcriptionally active chromatin, pieces of RNA export machinery and nuclear pore complexes (NPC), forms large aggregates called heavy chromatin.6 Besides, the expression of long genes containing internal repeats is markedly reduced in tho2 mutants.7


The yeast THO complex forms a 5-subunit assembly that directly interacts with active chromatin.

Gewartowski K, Cuéllar J, Dziembowski A, Valpuesta JM - Bioarchitecture (2012)

Figure 1. The THO complex couples RNA transcription elongation, mRNP formation and export. The THO binds active chromatin promoting association of Sub2 and Yra1 with the mRNP particle what facilitates mRNP export and prevents RNA/DNA hybrid formation (R-loops).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3675074&req=5

Figure 1: Figure 1. The THO complex couples RNA transcription elongation, mRNP formation and export. The THO binds active chromatin promoting association of Sub2 and Yra1 with the mRNP particle what facilitates mRNP export and prevents RNA/DNA hybrid formation (R-loops).
Mentions: Transcription of pre-mRNA, its maturation and mRNA export to the cytoplasm are a chain of processes involving cooperation of many proteins and assemblies. Over the years these processes have been intensively, albeit independently investigated. However, the acquired knowledge has led to a new vision of these processes as working in a coordinated manner. One of the examples of the connection between all the steps involved in RNA biogenesis is the role of the THO complex, thought to be formed by Tho2 (180 kDa), Hpr1 (90 kDa), Mft1 (45 kDa), and Thp2 (30 kDa) proteins.1 During transcription elongation, the THO complex is involved in packing pre-mRNA molecules into RNA–protein assemblies termed mRNPs2 and is also essential for efficient co-transcriptional recruitment of mRNA export factors Yra1 and Sub23 (Fig. 1). Disruption of any of these tightly coupled steps of production of translation-competent mRNA in the cytoplasm leads to the activation of the RNA surveillance pathway and to the subsequent degradation of non-active mRNA molecules.4 Lack of any of the THO subunits in yeast results in several molecular phenotypes like impairment of mRNP formation, that in turn leads to defects in transcription elongation and export. Lack of the Hpr1 subunit causes mRNA to remain trapped in the transcription sites giving rise to RNA/DNA hybrids (R-loops), which causes hyperrecombination and genomic instability.5 Deletion of the Mtf1 subunit promotes the accumulation of transcribed but not matured and exported RNA, which, together with transcriptionally active chromatin, pieces of RNA export machinery and nuclear pore complexes (NPC), forms large aggregates called heavy chromatin.6 Besides, the expression of long genes containing internal repeats is markedly reduced in tho2 mutants.7

Bottom Line: Recent data indicates that the THO complex is necessary for the proper expression of some genes, assurance of genetic stability by preventing transcription-associated recombination.We discuss the consequences of THO interaction with nucleic acids through the unfolded C-terminal region of Tho2, highlighting the importance of unfolded regions in eukaryotic proteins.Finally, we comment on THO recruitment to active chromatin, a role that is linked to mRNA biogenesis.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biochemistry and Biophysics; Polish Academy of Sciences; Warsaw, Poland; Department of Genetics and Biotechnology; Faculty of Biology; University of Warsaw; Warsaw, Poland.

ABSTRACT
The THO complex is a nuclear structure whose architecture is conserved among all kingdoms and plays an important role in mRNP biogenesis connecting transcription elongation with mRNA maturation and export. Recent data indicates that the THO complex is necessary for the proper expression of some genes, assurance of genetic stability by preventing transcription-associated recombination. Yeast THO has been described as a heterotetramer (Tho2, Hpr1, Mft1 and Thp2) that performs several functions through the interaction with other proteins like Tex1 or the mRNA export factors Sub2 and Yra1, with which it forms the TRanscription and EXport complex (TREX). In this article we review the cellular role of THO, which we show to be composed of five subunits with Tex1 being also an integral part of the complex. We also show a low-resolution structure of THO and localize some of its components. We discuss the consequences of THO interaction with nucleic acids through the unfolded C-terminal region of Tho2, highlighting the importance of unfolded regions in eukaryotic proteins. Finally, we comment on THO recruitment to active chromatin, a role that is linked to mRNA biogenesis.

Show MeSH
Related in: MedlinePlus