A Retinoblastoma Orthologue Is a Major Regulator of S-Phase, Mitotic, and Developmental Gene Expression in Dictyostelium

Adriano Ceccarelli,Kimchi Strasser,Harry Macwilliams,Adrian Tsang,Gareth Bloomfield,Juan Mata,Asa Macwilliams

doi:10.1371/journal.pone.0039914

Abstract

BackgroundThe retinoblastoma tumour suppressor, Rb, has two major functions. First, it represses genes whose products are required for S-phase entry and progression thus stabilizing cells in G1. Second, Rb interacts with factors that induce cell-cycle exit and terminal differentiation. Dictyostelium lacks a G1 phase in its cell cycle but it has a retinoblastoma orthologue, rblA. Methodology/Principal FindingsUsing microarray analysis and mRNA-Seq transcriptional profiling, we show that RblA strongly represses genes whose products are involved in S phase and mitosis. Both S-phase and mitotic genes are upregulated at a single point in late G2 and again in mid-development, near the time when cell cycling is reactivated. RblA also activates a set of genes unique to slime moulds that function in terminal differentiation.ConclusionsLike its mammalian counterpart Dictyostelium, RblA plays a dual role, regulating cell-cycle progression and transcriptional events leading to terminal differentiation. In the absence of a G1 phase, however, RblA functions in late G2 controlling the expression of both S-phase and mitotic genes.

Highlights

Dictyostelium is not a traditional model system for cell-cycle studies
Like its mammalian counterpart Dictyostelium, RblA plays a dual role, regulating cell-cycle progression and transcriptional events leading to terminal differentiation
In the absence of a G1 phase, RblA functions in late G2 controlling the expression of both S-phase and mitotic genes

Summary

Introduction

Most of the work done on the cell cycle of this organism was motivated by other questions, the desire to understand Dictyostelium development. In the latter process, amoebae differentiate into either stalk cells or spores. Pathway choice is determined by the cell-cycle position when development begins [1]. The G1/S transition is the major point at which the cell cycle is controlled in most eukaryotes. The retinoblastoma tumour suppressor, Rb, has two major functions. It represses genes whose products are required for S-phase entry and progression stabilizing cells in G1. Dictyostelium lacks a G1 phase in its cell cycle but it has a retinoblastoma orthologue, rblA

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Conclusion