The STAR protein, GLD-1, is a translational regulator of sexual identity in Caenorhabditis elegans

Jan, Eric; Motzny, Cynthia K.; Graves, Laura E.; Goodwin, Elizabeth B.

doi:10.1093/emboj/18.1.258

Cited by 230 publications

(181 citation statements)

References 61 publications

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“…GLD-1, another STAR/GSG protein, also has a binding site (UACU(A/C)A) that is almost identical to the BPS (55,56). GLD-1 is a Caenorhabditis elegans protein involved in germ line development and apoptosis that represses translation of such mRNAs as tra-2 and cep-1/p53 (57)(58)(59)(60). GLD-1 and BBP also have a 70% sequence identity and 85% sequence similarity in their RNA binding amino acids.…”

Section: Specificity Of Bbp Compared With Other Kh Domain Proteins-mentioning

confidence: 99%

An Extended RNA Binding Site for the Yeast Branch Point-binding Protein and the Role of Its Zinc Knuckle Domains in RNA Binding

Garrey¹,

Voelker²,

Berglund

2006

Journal of Biological Chemistry

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The highly conserved branch point sequence (BPS) of UAC-UAAC in Saccharomyces cerevisiae is initially recognized by the branch point-binding protein (BBP). Using systematic evolution of ligands by exponential enrichment we have determined that yeast BBP binds the branch point sequence UACUAAC with highest affinity and prefers an additional adenosine downstream of the BPS. Furthermore, we also found that a stem-loop upstream of the BPS enhances binding both to an artificially designed RNA (30-fold effect) and to an RNA from a yeast intron (3-fold effect). The zinc knuckles of BBP are partially responsible for the enhanced binding to the stem-loop but do not appear to have a significant role in the binding of BBP to single-strand RNA substrates. C-terminal deletions of BBP reveal that the linker regions between the two zinc knuckles and between the N-terminal RNA binding domains (KH and QUA2 domains) and the first zinc knuckle are important for binding to RNA. The lack of involvement of the second highly conserved zinc knuckle in RNA binding suggests that this zinc knuckle plays a different role in RNA processing than enhancing the binding of BBP to the BPS.The branch point-binding protein (BBP) 4 in Saccharomyces cerevisiae is an RNA-binding protein that is thought to be the first protein to bind the branch point sequence (BPS) during splicing. In yeast BBP binds to the highly invariant branch point sequence UACUAAC (branch point A is underlined), recognizing every nucleotide (1). BBP binds the BPS in the second commitment complex (CC2) and is necessary for stable formation of this complex (2). Splicing factor 1 (SF1), the human orthologue of BBP, is a more promiscuous RNA-binding protein, recognizing a degenerate sequence, CURAY (R ϭ purine, Y ϭ pyrimidine), in which only the U and A are critical (1). When discussing the yeast branch point-binding protein we will use the term BBP, when discussing the human protein we will use the term SF1, and when discussing both proteins we will use the term BBP/SF1. In the mammalian system, the equivalent complex to the yeast CC2 is the E complex in which SF1 binds the BPS (3, 4). In addition to recognizing the BPS, BBP/SF1 plays an important role in bridging the 5Ј end and 3Ј end of the intron by interacting with U1 snRNP at the 5Ј splice site and Mud2p at the 3Ј end of yeast introns and U2AF65 at the 3Ј end of human introns (5-8). BBP/SF1 is replaced at the BPS by U2 snRNP in an ATP-dependent step that leads to the formation of A complex (9, 10).BBP/SF1 contains multiple domains, many of which are conserved between yeast and human (Fig. 1). The BBP/SF1 N-terminal domain interacts with Mud2p in yeast and U2AF65 in humans (5,6,8). The C terminus contains a proline-rich domain, which in yeast interacts with Prp40, a component of the U1 snRNP (7). FBP11, a potential vertebrate homologue of Prp40, binds to the proline-rich domain of human SF1 (11).One of the most highly conserved regions of BBP/SF1 encompasses the RNA binding domains (Fig. 1). The region of BBP/SF1 responsible...

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Section: Specificity Of Bbp Compared With Other Kh Domain Proteins-mentioning

confidence: 99%

An Extended RNA Binding Site for the Yeast Branch Point-binding Protein and the Role of Its Zinc Knuckle Domains in RNA Binding

Garrey¹,

Voelker²,

Berglund

2006

Journal of Biological Chemistry

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“…They bind RNA through a GSG (Grp33/Sam68/GLD-1) domain, which contains a single KH domain (hnRNP K homology domain) flanked by conserved N-and C-terminal sequences named QUA1 and QUA2 domains required for homodimerization and specificity in RNA binding (Vernet and Artzt, 1997;Lukong and Richard, 2003). Interestingly, GLD-1, a STAR protein of C. elegans, is a temporal regulator of sexual identity and it is necessary for meiotic prophase progression of germ cells (Francis et al, 1995;Jan et al, 1999;Goodwin and Ellis, 2002). Accumulation of GLD-1 is required to switch from proliferation to meiosis during gametogenesis (Marin and Evans, 2003;Hansen et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

The Nuclear RNA-binding Protein Sam68 Translocates to the Cytoplasm and Associates with the Polysomes in Mouse Spermatocytes

Paronetto

Zalfa

Botti

et al. 2006

MBoC

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Translational control plays a crucial role during gametogenesis in organisms as different as worms and mammals. Mouse knockout models have highlighted the essential function of many RNA-binding proteins during spermatogenesis. Herein we have investigated the expression and function during mammalian male meiosis of Sam68, an RNA-binding protein implicated in several aspects of RNA metabolism. Sam68 expression and localization within the cells is stage specific: it is expressed in the nucleus of spermatogonia, it disappears at the onset of meiosis (leptotene/zygotene stages), and it accumulates again in the nucleus of pachytene spermatocytes and round spermatids. During the meiotic divisions, Sam68 translocates to the cytoplasm where it is found associated with the polysomes. Translocation correlates with serine/ threonine phosphorylation and it is blocked by inhibitors of the mitogen activated protein kinases ERK1/2 and of the maturation promoting factor cyclinB-cdc2 complex. Both kinases associate with Sam68 in pachytene spermatocytes and phosphorylate the regulatory regions upstream and downstream of the Sam68 RNA-binding motif. Molecular cloning of the mRNAs associated with Sam68 in mouse spermatocytes reveals a subset of genes that might be posttranscriptionally regulated by this RNA-binding protein during spermatogenesis. We also demonstrate that Sam68 shuttles between the nucleus and the cytoplasm in secondary spermatocytes, suggesting that it may promote translation of specific RNA targets during the meiotic divisions.

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“…Indeed, two regulatory branches control meiotic entry (Kadyk and Kimble 1998) and FBF represses an mRNA in each branch (Crittenden et al 2002;Eckmann et al 2004). One branch includes GLD-1, a translational repressor ( Jan et al 1999;Lee and Schedl 2001;Marin and Evans 2003), and the other branch consists of GLD-2/ GLD-3, a translational activator and poly(A) polymerase (Wang et al 2002;Suh et al 2006). Meiotic entry is dramatically curtailed in double mutants that delete key components of both branches, but not in the single mutants (Kadyk and Kimble 1998;Eckmann et al 2004;Hansen et al 2004b).…”

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confidence: 99%

FBF and Its Dual Control of gld-1 Expression in the Caenorhabditis elegans Germline

Suh

Crittenden

Goldstrohm³

et al. 2009

Genetics

125

168

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FBF, a PUF RNA-binding protein, is a key regulator of the mitosis/meiosis decision in the Caenorhabditis elegans germline. Genetically, FBF has a dual role in this decision: it maintains germ cells in mitosis, but it also facilitates entry into meiosis. In this article, we explore the molecular basis of that dual role. Previous work showed that FBF downregulates gld-1 expression to promote mitosis and that the GLD-2 poly(A) polymerase upregulates gld-1 expression to reinforce the decision to enter meiosis. Here we ask whether FBF can act as both a negative regulator and a positive regulator of gld-1 expression and also investigate its molecular mechanisms of control. We first show that FBF co-immunoprecipitates with gld-1 mRNA, a result that complements previous evidence that FBF directly controls gld-1 mRNA. Then we show that FBF represses gld-1 expression, that FBF physically interacts with the CCF-1/Pop2p deadenylase and can stimulate deadenylation in vitro, and that CCF-1 is partially responsible for maintaining low GLD-1 in the mitotic region. Finally, we show that FBF can elevate gld-1 expression, that FBF physically interacts with the GLD-2 poly(A) polymerase, and that FBF can enhance GLD-2 poly(A) polymerase activity in vitro. We propose that FBF can affect polyadenylation either negatively by its CCF-1 interaction or positively by its GLD-2 interaction.

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The STAR protein, GLD-1, is a translational regulator of sexual identity in Caenorhabditis elegans

Cited by 230 publications

References 61 publications

An Extended RNA Binding Site for the Yeast Branch Point-binding Protein and the Role of Its Zinc Knuckle Domains in RNA Binding

An Extended RNA Binding Site for the Yeast Branch Point-binding Protein and the Role of Its Zinc Knuckle Domains in RNA Binding

The Nuclear RNA-binding Protein Sam68 Translocates to the Cytoplasm and Associates with the Polysomes in Mouse Spermatocytes

FBF and Its Dual Control of gld-1 Expression in the Caenorhabditis elegans Germline

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