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人类细胞核和线粒体tRNA 3'加工的分子基础。

Molecular basis of human nuclear and mitochondrial tRNA 3' processing.

作者信息

Bhatta Arjun, Kuhle Bernhard, Yu Ryan D, Spanaus Lucas, Ditter Katja, Bohnsack Katherine E, Hillen Hauke S

机构信息

Department of Cellular Biochemistry, University Medical Center Göttingen, Göttingen, Germany.

Research Group Structure and Function of Molecular Machines, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.

出版信息

Nat Struct Mol Biol. 2025 Apr;32(4):613-624. doi: 10.1038/s41594-024-01445-w. Epub 2025 Jan 2.

DOI:10.1038/s41594-024-01445-w
PMID:39747487
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11996679/
Abstract

Eukaryotic transfer RNA (tRNA) precursors undergo sequential processing steps to become mature tRNAs. In humans, ELAC2 carries out 3' end processing of both nucleus-encoded (nu-tRNAs) and mitochondria-encoded (mt-tRNAs) tRNAs. ELAC2 is self-sufficient for processing of nu-tRNAs but requires TRMT10C and SDR5C1 to process most mt-tRNAs. Here we show that TRMT10C and SDR5C1 specifically facilitate processing of structurally degenerate mt-tRNAs lacking the canonical elbow. Structures of ELAC2 in complex with TRMT10C, SDR5C1 and two divergent mt-tRNA substrates reveal two distinct mechanisms of pre-tRNA recognition. While canonical nu-tRNAs and mt-tRNAs are recognized by direct ELAC2-RNA interactions, processing of noncanonical mt-tRNAs depends on protein-protein interactions between ELAC2 and TRMT10C. These results provide the molecular basis for tRNA 3' processing in both the nucleus and the mitochondria and explain the organelle-specific requirement for additional factors. Moreover, they suggest that TRMT10C-SDR5C1 evolved as a mitochondrial tRNA maturation platform to compensate for the structural erosion of mt-tRNAs in bilaterian animals.

摘要

真核生物转运RNA（tRNA）前体要经过一系列加工步骤才能成为成熟的tRNA。在人类中，ELAC2负责对细胞核编码的tRNA（nu-tRNAs）和线粒体编码的tRNA（mt-tRNAs）进行3'端加工。ELAC2在加工nu-tRNAs时无需其他因子，但加工大多数mt-tRNAs时需要TRMT10C和SDR5C1。我们在此表明，TRMT10C和SDR5C1专门促进缺乏典型肘部结构的结构退化型mt-tRNAs的加工。ELAC2与TRMT10C、SDR5C1以及两种不同的mt-tRNA底物形成的复合物结构揭示了前体tRNA识别的两种不同机制。典型的nu-tRNAs和mt-tRNAs通过ELAC2与RNA的直接相互作用被识别，而非典型mt-tRNAs的加工则依赖于ELAC2与TRMT10C之间的蛋白质-蛋白质相互作用。这些结果为细胞核和线粒体中tRNA的3'端加工提供了分子基础，并解释了对其他因子的细胞器特异性需求。此外，它们表明TRMT10C-SDR5C1演化为线粒体tRNA成熟平台，以补偿两侧对称动物中mt-tRNAs的结构退化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa1c/11996679/28cf6c43ad32/41594_2024_1445_Fig16_ESM.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa1c/11996679/0c0ef0f0403f/41594_2024_1445_Fig8_ESM.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa1c/11996679/28cf6c43ad32/41594_2024_1445_Fig16_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa1c/11996679/cd9beaa802d0/41594_2024_1445_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa1c/11996679/9ed938cdf055/41594_2024_1445_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa1c/11996679/16eb43bce0aa/41594_2024_1445_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa1c/11996679/4b7cd2c8c056/41594_2024_1445_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa1c/11996679/147f1b0dfadb/41594_2024_1445_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa1c/11996679/a1b86ded8830/41594_2024_1445_Fig7_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa1c/11996679/0c0ef0f0403f/41594_2024_1445_Fig8_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa1c/11996679/9b055615aa97/41594_2024_1445_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa1c/11996679/f72a6550adf3/41594_2024_1445_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa1c/11996679/1362c1c03b06/41594_2024_1445_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa1c/11996679/048e6f37406d/41594_2024_1445_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa1c/11996679/dafab7a2ef18/41594_2024_1445_Fig13_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa1c/11996679/eb2efb0db246/41594_2024_1445_Fig14_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa1c/11996679/98cdfa3bc048/41594_2024_1445_Fig15_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa1c/11996679/28cf6c43ad32/41594_2024_1445_Fig16_ESM.jpg

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