The C. elegans Homolog of RBBP6 (RBPL-1) Regulates Fertility through Controlling Cell Proliferation in the Germline and Nutrient Synthesis in the Intestine

Bob Goldstein,Ping Huang,Long Miao,Yanmei Zhao,Xuan Ma

doi:10.1371/journal.pone.0058736

Abstract

RBBP6 (retinoblastoma binding protein 6, also known as PACT or P2P-R in humans) is a multi-domain protein that functions in multiple processes, such as mitosis, cell differentiation, and cell apoptosis. RBBP6 is evolutionarily conserved and is present in unicellular organisms to mammals. Studies of RBBP6 have mostly focused on its RB- and p53-binding domains, which are found exclusively in mammals. Here, we investigated the C. elegans homolog of RBBP6 to explore the functional roles of its other domains. We found that RBPL-1, the homolog of RBBP6 in C. elegans, is indispensable for worm development. RNAi silencing of rbpl-1 led to embryonic lethality, as well as defects in oocyte production and intestine development. rbpl-1 RNAi worms showed defects in germ cell proliferation, suggesting that RBPL-1 regulates mitosis. Moreover, RNAi silencing of rbpl-1 inhibited nutrient synthesis in the worm intestine. RBPL-1, as a nucleolus protein, was found to be expressed in diverse tissues and necessary for both germline and soma development. Using microarray analysis, we identified ≈700 genes whose expression levels were changed at least 10-fold in rbpl-1 worms. We propose that RBPL-1, like its yeast homolog, may regulate gene expression as an mRNA cleavage and polyadenylation factor. Taken together, the findings from this study reveal that RBPL-1 plays a pivotal role in C. elegans germline and soma development, suggesting that the functions of RBBP6 are conserved in diverse eukaryotic species.

Highlights

RBBP6 was first identified in mouse testis and was implicated in controlling cell proliferation and differentiation [1]
We identified the sole homolog of mammalian RBBP6 in C. elegans, RBPL-1, and characterized the roles it plays in C. elegans development
We show that RBPL-1 regulates nutrient synthesis in the intestine and germ-cell proliferation, which is reminiscent of its mammalian homolog P2P-R who is involved in mitosis

Summary

Introduction

RBBP6 was first identified in mouse testis and was implicated in controlling cell proliferation and differentiation [1]. It is an evolutionarily conserved 250-kDa multi-domain protein present in a wide variety of eukaryotic organisms ranging from microsporidia, to plants, to vertebrates. RBBP6 is composed of six domains– a DWNN, zinc knuckle, RING finger, SR, Rb, and a p53-binding domain–in vertebrates [2], while its homologs in all other species lack the Rb and p53-binding domains. RBBP6 controls a wide range of biological processes, such as mitosis, mRNA processing, ubiquitination, and translation [1,2,3,4,5]. RBBP6 was recently proposed to be a U-box protein with a role in controlling protein degradation [10]

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Conclusion