DLP, a Novel Dim1 Family Protein Implicated in Pre-mRNA Splicing and Cell Cycle Progression

Subnuclear organization and spatiotemporal regulation of pre-mRNA processing factors is essential for the production of mature protein-coding mRNAs. We have discovered that a large protein called Son has a novel role in maintaining proper nuclear organization of pre-mRNA processing factors in nuclear speckles. The primary sequence of Son contains a concentrated region of multiple unique tandem repeat motifs that may support a role for Son as a scaffolding protein for RNA processing factors in nuclear speckles. We used RNA interference (RNAi) approaches and high-resolution microscopy techniques to study the functions of Son in the context of intact cells. Although Son precisely colocalizes with pre-mRNA splicing factors in nuclear speckles, its depletion by RNAi leads to cell cycle arrest in metaphase and causes dramatic disorganization of small nuclear ribonuclear protein and serine-arginine rich protein splicing factors during interphase. Here, we propose that Son is essential for appropriate subnuclear organization of pre-mRNA splicing factors and for promoting normal cell cycle progression.

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Genetic and Physical Interactions Between Factors Involved in Both Cell Cycle Progression and Pre-mRNA Splicing inSaccharomyces cerevisiae

Genetics ◽

10.1093/genetics/156.4.1503 ◽

2000 ◽

Vol 156 (4) ◽

pp. 1503-1517 ◽

Cited By ~ 2

Author(s):

Sigal Ben-Yehuda ◽

Ian Dix ◽

Caroline S Russell ◽

Margaret McGarvey ◽

Jean D Beggs ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Progression ◽

Synthetic Lethality ◽

Mrna Splicing ◽

Splicing Factors ◽

Restrictive Temperature ◽

Cycle Progression ◽

Cellular Processes ◽

Physical Interactions ◽

Mutant Cells

AbstractThe PRP17/CDC40 gene of Saccharomyces cerevisiae functions in two different cellular processes: pre-mRNA splicing and cell cycle progression. The Prp17/Cdc40 protein participates in the second step of the splicing reaction and, in addition, prp17/cdc40 mutant cells held at the restrictive temperature arrest in the G2 phase of the cell cycle. Here we describe the identification of nine genes that, when mutated, show synthetic lethality with the prp17/cdc40Δ allele. Six of these encode known splicing factors: Prp8p, Slu7p, Prp16p, Prp22p, Slt11p, and U2 snRNA. The other three, SYF1, SYF2, and SYF3, represent genes also involved in cell cycle progression and in pre-mRNA splicing. Syf1p and Syf3p are highly conserved proteins containing several copies of a repeated motif, which we term RTPR. This newly defined motif is shared by proteins involved in RNA processing and represents a subfamily of the known TPR (tetratricopeptide repeat) motif. Using two-hybrid interaction screens and biochemical analysis, we show that the SYF gene products interact with each other and with four other proteins: Isy1p, Cef1p, Prp22p, and Ntc20p. We discuss the role played by these proteins in splicing and cell cycle progression.

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