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The pre-mRNA retention and splicing complex controls tRNA maturation by promoting TAN1 expression
Yang Zhou1, Changchun Chen, Marcus J O Johansson
1Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden.
Nucleic Acids Research
|April 23, 2013
Summary
The pre-mRNA retention and splicing (RES) complex is crucial for tRNA modification. Its absence impairs N(4)-acetylcytidine (ac(4)C) formation by affecting TAN1 pre-mRNA splicing.
Area of Science:
- Molecular Biology
- RNA Biology
- Gene Expression
Background:
- The pre-mRNA retention and splicing (RES) complex, comprising Bud13p, Snu17p, and Pml1p in yeast, is implicated in nuclear retention and splicing of pre-mRNAs.
- The modified nucleoside N(4)-acetylcytidine (ac(4)C) is essential for tRNA function and is found at position 12 in specific serine and leucine tRNAs.
Purpose of the Study:
- To investigate the role of the RES complex in the biogenesis of ac(4)C-modified tRNAs.
- To elucidate the mechanism by which RES factors influence ac(4)C formation.
Main Methods:
- Analysis of ac(4)C levels in wild-type and RES-deficient yeast strains.
- Investigation of TAN1 pre-mRNA splicing efficiency and stability.
- Identification of cis-acting elements within TAN1 pre-mRNA required for RES dependency.
- Assessment of TAN1 pre-mRNA localization and degradation pathways.
Main Results:
- Absence of Bud13p or Snu17p significantly reduces ac(4)C levels, while Pml1p deficiency impacts ac(4)C at higher temperatures.
- RES complex deficiency leads to inefficient splicing of TAN1 pre-mRNA, resulting in reduced Tan1p levels.
- The intron sequence of TAN1 pre-mRNA is essential and sufficient for RES-dependent processing.
- TAN1 pre-mRNA is susceptible to nonsense-mediated mRNA decay in RES-deficient cells, suggesting impaired nuclear retention.
Conclusions:
- The RES complex plays a critical, previously unrecognized role in the processing of TAN1 pre-mRNA.
- Efficient TAN1 pre-mRNA splicing by the RES complex is necessary for proper ac(4)C modification in tRNA.
- RES-mediated nuclear retention of TAN1 pre-mRNA may be crucial for preventing its degradation and ensuring correct tRNA modification.
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