Non-LTR retrotransposons encode noncanonical RRM domains in their first open reading frame

被引:102
作者
Khazina, Elena [1 ]
Weichenrieder, Oliver [1 ]
机构
[1] Max Planck Inst Dev Biol, Dept Biochem, D-72076 Tubingen, Germany
关键词
genome evolution; LINE-1; nucleic acid chaperone; RNP; crystal structure; RIBONUCLEOPROTEIN PARTICLE FORMATION; RNA-BINDING PROTEINS; ORF1; PROTEIN; REVERSE TRANSCRIPTION; TRANSPOSABLE ELEMENTS; CHAPERONE ACTIVITY; LINE-1; GAG PROTEINS; TARGET SITE; I-FACTOR;
D O I
10.1073/pnas.0809964106
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Non-LTR retrotransposons (NLRs) are a unique class of mobile genetic elements that have significant impact on the evolution of eukaryotic genomes. However, the molecular details and functions of their encoded proteins, in particular of the accessory ORF1p proteins, are poorly understood. Here, we identify noncanonical RNA-recognition-motifs (RRMs) in several phylogenetically unrelated NLR ORF1p proteins. This provides an explanation for their RNA-binding properties and clearly shows that they are not related to the retroviral nucleocapsid protein Gag, despite the frequent presence of CCHC zinc knuckles. In particular, we characterize the ORF1p protein of the human long interspersed nuclear element 1 (LINE-1 or L1). We show that L1ORF1p is a multidomain protein, consisting of a coiled coil (cc), RRM, and C-terminal domain (CTD). Most importantly, we solved the crystal structure of the RRM domain, which is characterized by extended loops stabilized by unique salt bridges. Furthermore, we demonstrate that L1ORF1p trimerizes via its N-terminal cc domain, and we suggest that this property is functionally important for all homologues. The formation of distinct complexes with single-stranded nucleic acids requires the presence of the RRM and CTD domains on the same polypeptide chain as well as their close cooperation. Finally, the phylogenetic analysis of mammalian L1ORF1p shows an ancient origin of the RRM domain and supports a modular evolution of NLRs.
引用
收藏
页码:731 / 736
页数:6
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