Phylogenetic comparison and splice site conservation of eukaryotic U1 snRNP-specific U1-70K gene family

Tao Fan,Yuan Tian,Das Debatosh,Chen Chen,Yu-Zhen Zhao,Jianhua Zhang,Ying-Gao Liu,Shao-Ming Zhou,Qin-Lai Liu,Mo-Xian Chen,Jing-Fang Yang

doi:10.1038/s41598-021-91693-3

Abstract

Eukaryotic cells can expand their coding ability by using their splicing machinery, spliceosome, to process precursor mRNA (pre-mRNA) into mature messenger RNA. The mega-macromolecular spliceosome contains multiple subcomplexes, referred to as small nuclear ribonucleoproteins (snRNPs). Among these, U1 snRNP and its central component, U1-70K, are crucial for splice site recognition during early spliceosome assembly. The human U1-70K has been linked to several types of human autoimmune and neurodegenerative diseases. However, its phylogenetic relationship has been seldom reported. To this end, we carried out a systemic analysis of 95 animal U1-70K genes and compare these proteins to their yeast and plant counterparts. Analysis of their gene and protein structures, expression patterns and splicing conservation suggest that animal U1-70Ks are conserved in their molecular function, and may play essential role in cancers and juvenile development. In particular, animal U1-70Ks display unique characteristics of single copy number and a splicing isoform with truncated C-terminal, suggesting the specific role of these U1-70Ks in animal kingdom. In summary, our results provide phylogenetic overview of U1-70K gene family in vertebrates. In silico analyses conducted in this work will act as a reference for future functional studies of this crucial U1 splicing factor in animal kingdom.

Highlights

Precursor-mRNA splicing is a crucial eukaryotic molecular mechanism which was discovered nearly half a century ago[1]
The obtained sequences consisting of both PF00076.22 (RNA recognition motif, RRM_1) and PF12220.8 (U1 small nuclear ribonucleoprotein of 70 kDa MW N terminal, U1snRNP70_N) protein domains were further screened by HMMER
A total of 95 U1-70K genes were identified from 95 animal species (Table S1), including 23 primates, 36 rodents and lagomorphs, 17 other mammals, 14 other vertebrates and 5 other species (Ciona intestinalis, Ciona savignyi, Caenorhabditis elegans, Drosophila melanogaster and Saccharomyces cerevisiae)

Summary

Introduction

Precursor-mRNA splicing is a crucial eukaryotic molecular mechanism which was discovered nearly half a century ago[1]. A significant association between the co-existence of antibodies to cytomegalovirus (CMV) and snRNPs has been observed in SLE patients[22], suggesting the crosstalk between CMV and autoimmunity of SLE Besides these autoimmune diseases, neurodegenerative diseases such as Alzheimer’s disease (AD) may result from splicing defects due to disruption in U1 snRNPs. Pathological evidence of human brain-insoluble proteome has demonstrated the unique aggregation pattern of U1 snRNPs in AD diseased neuronal c ells[23], causing global splicing defects in the early stages of AD in the affected patients. U1snRNPs such as U1-70K can be considered to be a crucial regulator of a variety of human diseases and the study of its phylogeny and splicing pattern may help us to identify the potential molecular function of this splicing factor To this end, we carried out a phylogenetic analysis of 95 species/strains available on the Ensemble database (http://asia.ensembl.org/index.html). The outcome of this study should provide readers with a background information of this gene family which could be used for further functional investigations

Methods

Results

Discussion

Conclusion