Human ERAL1 is a mitochondrial RNA chaperone involved in the assembly of the 28S small mitochondrial ribosomal subunit.
Human ERAL1 is a mitochondrial RNA chaperone involved in the assembly of the 28S small mitochondrial ribosomal subunit.
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DOI：
10.1042/bj20100757
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发表时间：
2010-09-15
期刊：
影响因子：
--
通讯作者：
Lightowlers RN
中科院分区：
文献类型：
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作者：
Dennerlein S;Rozanska A;Wydro M;Chrzanowska-Lightowlers ZM;Lightowlers RN
细菌Ras样蛋白Era先前已被报道结合30 S核糖体亚基内的16 S rRNA，并在核糖体组装中发挥关键作用。这种必需的GTMERAL 1（Era G蛋白样1）的直向同源物存在于高等真核生物中，尽管其确切的分子功能和细胞定位尚不清楚，但其缺失与细胞凋亡有关。在本研究中，我们表明，人类ERAL 1是一个线粒体蛋白的重要形成的28 S小mitoribosomal亚基。我们还表明，ERAL 1结合在体内的小亚基[12 S mt（线粒体）-rRNA]的rRNA组分。细菌Era与紧邻16 S rRNA末端茎环（螺旋45）下游的3′非结构化九核苷酸结合。该位点包含在所有生命结构域中高度保守的AUCA序列，紧邻在细菌中保守的抗Shine-Dalgarno序列的上游。令人惊讶的是，这整个区域在12 S mt-rRNA中缺失。我们将ERAL 1结合位点定位在12 S mt-rRNA 3′端茎环区的一个33个核苷酸的区域。该环含有两个腺嘌呤残基，据报道在有丝分裂体成熟时被二甲基化。此外，与细菌直向同源物相比，ERAL 1的缺失导致新生12 S mt-rRNA的快速衰减，这与线粒体RNA伴侣的作用一致。最后，尽管ERAL 1的缺失导致细胞凋亡，但细胞死亡发生在线粒体蛋白质合成的任何明显损失或线粒体mRNA稳定性的降低之前。
The bacterial Ras-like protein Era has been reported previously to bind 16S rRNA within the 30S ribosomal subunit and to play a crucial role in ribosome assembly. An orthologue of this essential GTPase ERAL1 (Era G-protein-like 1) exists in higher eukaryotes and although its exact molecular function and cellular localization is unknown, its absence has been linked to apoptosis. In the present study we show that human ERAL1 is a mitochondrial protein important for the formation of the 28S small mitoribosomal subunit. We also show that ERAL1 binds in vivo to the rRNA component of the small subunit [12S mt (mitochondrial)-rRNA]. Bacterial Era associates with a 3′ unstructured nonanucleotide immediately downstream of the terminal stem–loop (helix 45) of 16S rRNA. This site contains an AUCA sequence highly conserved across all domains of life, immediately upstream of the anti-Shine–Dalgarno sequence, which is conserved in bacteria. Strikingly, this entire region is absent from 12S mt-rRNA. We have mapped the ERAL1-binding site to a 33 nucleotide section delineating the 3′ terminal stem–loop region of 12S mt-rRNA. This loop contains two adenine residues that are reported to be dimethylated on mitoribosome maturation. Furthermore, and also in contrast with the bacterial orthologue, loss of ERAL1 leads to rapid decay of nascent 12S mt-rRNA, consistent with a role as a mitochondrial RNA chaperone. Finally, whereas depletion of ERAL1 leads to apoptosis, cell death occurs prior to any appreciable loss of mitochondrial protein synthesis or reduction in the stability of mitochondrial mRNA.