Yeast Rrp8p, a novel methyltransferase responsible for m1A 645 base modification of 25S rRNA.

Yeast Rrp8p, a novel methyltransferase responsible for m1A 645 base modification of 25S rRNA.
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DOI:
10.1093/nar/gks1102
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发表时间:
2013-01
影响因子:
14.9
通讯作者:
Entian KD
Entian KD
中科院分区:
生物学2区
文献类型:
--
作者:
Peifer C;Sharma S;Watzinger P;Lamberth S;Kötter P;Entian KD

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核糖体RNA经过各种修饰以优化核糖体结构并扩大RNA的拓扑潜力。核糖体RNA (rRNA)中最常见的核苷酸修饰是假尿嘧啶化和2 ' -O甲基化(Nm),分别由H/ACA盒snoRNAs和C/D盒snoRNAs进行。此外,这两种核糖体亚基的rnas也含有各种碱基修饰,这些修饰可以被特定的酶催化。这些修饰聚集在核糖体的高度保守区域。虽然大多数催化18S rRNA碱基修饰的酶已经被确定,但对25S rRNA碱基修饰知之甚少。在真核生物中,位于螺旋25.1中645位的m1A修饰是高度保守的。在25S rRNA的这一区域形成螺旋可能是5.8S rRNA与25S rRNA相互作用的正确拓扑框架的先决条件。令人惊讶的是,我们已经鉴定出核糖体RNA加工蛋白8 (Rrp8),一种核核罗斯曼折叠样甲基转移酶,在645位进行m1A碱基修饰,尽管Rrp8先前被证明参与A2切割和40S生物发生。此外,我们能够在Rrp8中鉴定出特定的点突变,这表明s -腺苷-蛋氨酸结合减少会影响60S亚基的质量。这突出了Rrp8在这两个亚基的生物发生中的双重功能。
Ribosomal RNA undergoes various modifications to optimize ribosomal structure and expand the topological potential of RNA. The most common nucleotide modifications in ribosomal RNA (rRNA) are pseudouridylations and 2′-O methylations (Nm), performed by H/ACA box snoRNAs and C/D box snoRNAs, respectively. Furthermore, rRNAs of both ribosomal subunits also contain various base modifications, which are catalysed by specific enzymes. These modifications cluster in highly conserved areas of the ribosome. Although most enzymes catalysing 18S rRNA base modifications have been identified, little is known about the 25S rRNA base modifications. The m1A modification at position 645 in Helix 25.1 is highly conserved in eukaryotes. Helix formation in this region of the 25S rRNA might be a prerequisite for a correct topological framework for 5.8S rRNA to interact with 25S rRNA. Surprisingly, we have identified ribosomal RNA processing protein 8 (Rrp8), a nucleolar Rossman-fold like methyltransferase, to carry out the m1A base modification at position 645, although Rrp8 was previously shown to be involved in A2 cleavage and 40S biogenesis. In addition, we were able to identify specific point mutations in Rrp8, which show that a reduced S-adenosyl-methionine binding influences the quality of the 60S subunit. This highlights the dual functionality of Rrp8 in the biogenesis of both subunits.
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