A retinoblastoma orthologue is a major regulator of S-phase, mitotic, and developmental gene expression in Dictyostelium

PLoS One. 2012;7(6):e39914. doi: 10.1371/journal.pone.0039914. Epub 2012 Jun 29.

Abstract

Background: The 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 findings: Using 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.

Conclusions: 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, however, RblA functions in late G2 controlling the expression of both S-phase and mitotic genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cold Temperature
  • Dictyostelium / cytology*
  • Dictyostelium / genetics*
  • Gene Expression Regulation, Developmental*
  • Gene Regulatory Networks / genetics
  • Genes, Developmental / genetics
  • Genes, Protozoan / genetics
  • Mitosis / genetics*
  • Models, Genetic
  • Oligonucleotide Array Sequence Analysis
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Retinoblastoma Protein / chemistry*
  • S Phase / genetics*
  • Sequence Homology, Amino Acid*

Substances

  • Protozoan Proteins
  • RNA, Messenger
  • Repressor Proteins
  • Retinoblastoma Protein