Structural basis for specific recognition of pre-snRNA by Gemin5

• Published in: Cell research 2016-12, Vol.26 (12), p.1353-1356
• Main Authors: Tang, Xuhua, Bharath, Sakshibeedu R, Piao, Shunfu, Tan, Vanessa Qianmin, Bowler, Matthew W, Song, Haiwei
• Format: Article
• Language: English
• Subjects: 631/337/384/521; 631/45/535; 631/45/612/1230; 631/80/86; Biomedical and Life Sciences; Cell Biology; Letter to the Editor; Life Sciences; snRNA
• ISSN: 1001-0602; 1748-7838
• DOI: 10.1038/cr.2016.133

Dear Editor, The survival of motor neurons （SMN） complex assembles the heptameric rings of Sm proteins （Sm core） on small nuclear RNAs （snRNAs） to form small nuclear ribonucleoprotein particles （snRNPs） [1-4], the major components of the spliceosome [5]. The SMN complex consists of SMN, Unrip and Gemin2-8 [6, 7]. SMN deficiency leads to correspondingly reduced snRNP assembly and is an underlying cause for spinal muscular atrophy, a common motor neuron degenerative disease [8]. The SMN complex functions to ensure Sm core assembly only on the correct snRNAs, therefore preventing aberrant Sm core formation. Such stringent specificity of the SMN complex toward snRNAs is conferred by Gemin5, which directly interacts with sn- RNA precursors （pre-snRNAs） [9-11] and delivers them to sites of Sm core assembly and processing. Gemin5 recognizes the snRNP code comprised of the Sm site （AU5-6G） and an adjacent Y-terminal stem loop via its N-terminal WD40 repeat domain （termed Gemin5-WD）. Gemin5 also has been shown to bind the 7-methylguanosine （m7G） cap [12] and to downregulate internal ribosome entry site-dependent translation [13]. Although the function of Gemin5 in the biogenesis of snRNPs has been explored, the molecular mechanism for specific recognition of pre-snRNAs by Gemin5 remains elusive.