A late-stage assembly checkpoint of the human mitochondrial ribosome large subunit.
A late-stage assembly checkpoint of the human mitochondrial ribosome large subunit.
复制标题
DOI：
10.1038/s41467-022-28503-5
复制
发表时间：
2022-02-17
影响因子：
16.6
通讯作者：
Minczuk M
中科院分区：
文献类型：
--
作者：
Rebelo-Guiomar P;Pellegrino S;Dent KC;Sas-Chen A;Miller-Fleming L;Garone C;Van Haute L;Rogan JF;Dinan A;Firth AE;Andrews B;Whitworth AJ;Schwartz S;Warren AJ;Minczuk M
许多细胞过程，包括核糖体生物合成，通过转录后RNA修饰来调节。在这里，人类线粒体转录组的全基因组分析表明，2 '-O-甲基化仅限于线粒体大亚基（mtLSU）16 S mt-rRNA的残基，由MRM 1，MRM 2和MRM 3引入，后两种蛋白质安装的修饰是相互依赖的。MRM 2通过调节线粒体生物合成来控制线粒体呼吸。在它的情况下，mtLSU颗粒（通过cryo-EM在2.6 μ m的分辨率下可视化）呈现无序的RNA结构域，bL 36 m的部分占据和结合的MALSU 1：L0 R8 F8：mtACP抗缔合模块，允许五个具有不同亚基间界面构型的mtLSU生物合成中间体沿组装途径沿着放置。然而，线粒体生物合成不依赖于MRM 2的甲基转移酶活性。破坏MRM 2果蝇直系同源物导致果蝇相关的发育停滞。这项工作确定了mtLSU组装过程中的一个关键检查点，对维持线粒体稳态至关重要。Rebelo-Guiomar等人通过使细胞中的甲基转移酶MRM 2失活来揭示人类线粒体核糖体的后期组装中间体。MRM 2的缺乏损害生物体内平衡，而其催化活性则不利于线粒体生物合成。
Many cellular processes, including ribosome biogenesis, are regulated through post-transcriptional RNA modifications. Here, a genome-wide analysis of the human mitochondrial transcriptome shows that 2’-O-methylation is limited to residues of the mitoribosomal large subunit (mtLSU) 16S mt-rRNA, introduced by MRM1, MRM2 and MRM3, with the modifications installed by the latter two proteins being interdependent. MRM2 controls mitochondrial respiration by regulating mitoribosome biogenesis. In its absence, mtLSU particles (visualized by cryo-EM at the resolution of 2.6 Å) present disordered RNA domains, partial occupancy of bL36m and bound MALSU1:L0R8F8:mtACP anti-association module, allowing five mtLSU biogenesis intermediates with different intersubunit interface configurations to be placed along the assembly pathway. However, mitoribosome biogenesis does not depend on the methyltransferase activity of MRM2. Disruption of the MRM2 Drosophila melanogaster orthologue leads to mitochondria-related developmental arrest. This work identifies a key checkpoint during mtLSU assembly, essential to maintain mitochondrial homeostasis. Rebelo-Guiomar et al. unveil late stage assembly intermediates of the human mitochondrial ribosome by inactivating the methyltransferase MRM2 in cells. Absence of MRM2 impairs organismal homeostasis, while its catalytic activity is dispensable for mitoribosomal biogenesis.
登录
查看更多内容
DOI：
10.1126/science.aaa1193
发表时间：
2015-04-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Amunts A;Brown A;Toots J;Scheres SHW;Ramakrishnan V
通讯作者：
Ramakrishnan V
影响因子：
16.6
作者：
Birkedal, Ulf;Christensen-Dalsgaard, Mikkel;Nielsen, Henrik
通讯作者：
Nielsen, Henrik
影响因子：
16.6
作者：
Cheng J;Berninghausen O;Beckmann R
通讯作者：
Beckmann R
DOI：
10.1126/science.1237973
发表时间：
2013-08-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Engreitz JM;Pandya-Jones A;McDonel P;Shishkin A;Sirokman K;Surka C;Kadri S;Xing J;Goren A;Lander ES;Plath K;Guttman M
通讯作者：
Guttman M
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH