Promoter-sharing by different genes in human genome – CPNE1 and RBM12 gene pair as an example

Wanling Yang,Minghui Zhao,Yu Lau,Siu-Ming Yiu,Ping Ng,Thomas Kf Wong

doi:10.1186/1471-2164-9-456

Wanling Yang, Minghui Zhao + Show 4 more

Open Access

https://doi.org/10.1186/1471-2164-9-456

Copy DOI

Abstract

BackgroundRegulation of gene expression plays important role in cellular functions. Co-regulation of different genes may indicate functional connection or even physical interaction between gene products. Thus analysis on genomic structures that may affect gene expression regulation could shed light on the functions of genes.ResultsIn a whole genome analysis of alternative splicing events, we found that two distinct genes, copine I (CPNE1) and RNA binding motif protein 12 (RBM12), share the most 5' exons and therefore the promoter region in human. Further analysis identified many gene pairs in human genome that share the same promoters and 5' exons but have totally different coding sequences. Analysis of genomic and expressed sequences, either cDNAs or expressed sequence tags (ESTs) for CPNE1 and RBM12, confirmed the conservation of this phenomenon during evolutionary courses. The co-expression of the two genes initiated from the same promoter is confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) in different tissues in both human and mouse. High degrees of sequence conservation among multiple species in the 5'UTR region common to CPNE1 and RBM12 were also identified.ConclusionPromoter and 5'UTR sharing between CPNE1 and RBM12 is observed in human, mouse and zebrafish. Conservation of this genomic structure in evolutionary courses indicates potential functional interaction between the two genes. More than 20 other gene pairs in human genome were found to have the similar genomic structure in a genome-wide analysis, and it may represent a unique pattern of genomic arrangement that may affect expression regulation of the corresponding genes.

Highlights

Regulation of gene expression plays important role in cellular functions
In a genome-wide analysis of alternative splicing gene variants by alignment of Expressed sequence tags (EST) and human genomic sequences[14], we have discovered that the human copine I (CPNE1) and RNA binding motif protein 12 (RBM12) gene often share 5'UTR sequences but do not show any protein coding sequence similarity
In this study, using CPNE1/ RBM12 gene pair as an example, we showed the conservation of the phenomenon in different species during evolutionary courses

Summary

Introduction

Regulation of gene expression plays important role in cellular functions. Coregulation of different genes may indicate functional connection or even physical interaction between gene products. Genes belonging to the same functional group tend to have similar expression patterns and share expression regulation mechanisms. This was found first in prokaryotes, in which genes of the same functional groups are transcribed into one polycistronic mRNA through an operon structure [1]. CPNE1 was first identified as a calciumdependent, phospholipids-binding protein, and it was thought to be involved in membrane trafficking [8]. It contains two calcium-binding, protein kinase C conserved region 2 domains (C2 domains) in the N-terminus and a domain similar to the von Willebrand factor type A domain (A domain) that mediates interactions between integrins and extracellular ligands in the C-terminus. While the exact function of CPNE1 is still not clear, it was shown that interaction with CPNE1 may result in recruitment of target proteins to membrane surfaces and regulation of the enzymatic activities of target proteins [9]

Methods

Results

Discussion

Conclusion