Muller Sébastien, Urban Alan, Hecker Arnaud, Leclerc Fabrice, Branlant Christiane, Motorin Yuri
Laboratoire de Maturation des ARN et Enzymologie Moléculaire, UMR 7567 CNRS-UHP Nancy Université, BP 239, 54506 Vandoeuvre-les-Nancy Cedex, France.
Nucleic Acids Res. 2009 Mar;37(4):1308-22. doi: 10.1093/nar/gkn1037. Epub 2009 Jan 12.
Up to now, Psi formation in tRNAs was found to be catalysed by stand-alone enzymes. By computational analysis of archaeal genomes we detected putative H/ACA sRNAs, in four Sulfolobales species and in Aeropyrum pernix, that might guide Psi 35 formation in pre-tRNA(Tyr)(GUA). This modification is achieved by Pus7p in eukarya. The validity of the computational predictions was verified by in vitro reconstitution of H/ACA sRNPs using the identified Sulfolobus solfataricus H/ACA sRNA. Comparison of Pus7-like enzymes encoded by archaeal genomes revealed amino acid substitutions in motifs IIIa and II in Sulfolobales and A. pernix Pus7-like enzymes. These conserved RNA:Psi-synthase- motifs are essential for catalysis. As expected, the recombinant Pyrococcus abyssi aPus7 was fully active and acted at positions 35 and 13 and other positions in tRNAs, while the recombinant S. solfataricus aPus7 was only found to have a poor activity at position 13. We showed that the presence of an A residue 3' to the target U residue is required for P. abyssi aPus7 activity, and that this is not the case for the reconstituted S. solfataricus H/ACA sRNP. In agreement with the possible formation of Psi 35 in tRNA(Tyr)(GUA) by aPus7 in P. abyssi and by an H/ACA sRNP in S. solfataricus, the A36G mutation in the P. abyssi tRNA(Tyr)(GUA) abolished Psi 35 formation when using P. abyssi extract, whereas the A36G substitution in the S. solfataricus pre-tRNA(Tyr) did not affect Psi 35 formation in this RNA when using an S. solfataricus extract.
到目前为止,人们发现tRNA中Psi的形成是由独立的酶催化的。通过对古菌基因组的计算分析,我们在四种硫化叶菌属物种和嗜火栖热菌中检测到了可能指导前体tRNA(Tyr)(GUA)中Psi 35形成的假定H/ACA sRNA。在真核生物中,这种修饰是由Pus7p完成的。通过使用鉴定出的嗜热栖热硫化叶菌H/ACA sRNA对H/ACA sRNP进行体外重组,验证了计算预测的有效性。对古菌基因组编码的Pus7样酶的比较揭示了硫化叶菌属和嗜火栖热菌Pus7样酶在基序IIIa和II中的氨基酸替换。这些保守的RNA:Psi合成酶基序对于催化作用至关重要。正如预期的那样,重组深渊栖热球菌aPus7具有完全活性,并作用于tRNA的35位和13位以及其他位置,而重组嗜热栖热硫化叶菌aPus7仅在13位表现出较弱的活性。我们表明,深渊栖热球菌aPus7活性需要在靶标U残基的3'端存在一个A残基,而重组嗜热栖热硫化叶菌H/ACA sRNP则并非如此。与深渊栖热球菌中的aPus7和嗜热栖热硫化叶菌中的H/ACA sRNP可能在tRNA(Tyr)(GUA)中形成Psi 35一致,当使用深渊栖热球菌提取物时,深渊栖热球菌tRNA(Tyr)(GUA)中的A36G突变消除了Psi 35的形成,而当使用嗜热栖热硫化叶菌提取物时,嗜热栖热硫化叶菌前体tRNA(Tyr)中的A36G替换并不影响该RNA中Psi 35的形成。