Building RNA–protein granules: insight from the germline

Arkov, Alexey L.; Ramos, Andrés

doi:10.1016/j.tcb.2010.05.004

Cited by 76 publications

(87 citation statements)

References 112 publications

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“…These proteins comprise over 90% of the total CB content by mass. Four of these proteins, MIWI, DDX4, TDRD6 and TDRD7 have been implicated in piRNA-mediated RNA regulation (Arkov & Ramos 2010, Kuramochi-Miyagawa et al 2010). In addition, MILI and TDRD1 have been localised to the CB by immunostaining experiments (Chuma et al 2006).…”

Section: Pachytene Pirnasmentioning

confidence: 99%

“…Despite the fact that the CB in mouse and the germ granules in lower organisms (fly, nematodes and frogs) apparently support different Chromatoid body and small RNAs biological functions, they still share many protein components. These include the DEAD-box RNA helicase Vasa (DDX4 or MVH in mouse), Tudor domain-containing proteins as well as PIWI proteins (Arkov & Ramos 2010). In Drosophila, the connection of small RNA-mediated gene silencing and germ granules (nuage) in the ovarian germ line has been nicely described.…”

Section: Pachytene Pirnasmentioning

confidence: 99%

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Chromatoid body and small RNAs in male germ cells

Meikar¹,

Ros²,

Korhonen³

et al. 2011

Reproduction

145

154

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The chromatoid body (CB) is a germ granule in the cytoplasm of postmeiotic haploid round spermatids that is loaded with RNA and RNAbinding proteins. Following the discovery of small non-coding RNA-mediated gene regulation and the identification of PIWI-interacting RNAs (piRNAs) that have crucial roles in germ line development, the function of the CB has slowly begun to be revealed. Male germ cells utilise small RNAs to control the complex and specialised process of sperm production. Several microRNAs have been identified during spermatogenesis. In addition, a high number of piRNAs are present both in embryonic and postnatal male germ cells, with their expression being impressively induced in late meiotic cells and haploid round spermatids. At postmeiotic stage of germ cell differentiation, the CB accumulates piRNAs and proteins of piRNA machinery, as well as several other proteins involved in distinct RNA regulation pathways. All existing evidence suggests a role for the CB in mRNA regulation and small RNA-mediated gene control, but the mechanisms remain uncharacterised. In this review, we summarise the current knowledge of the CB and its association with small RNA pathways.

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Section: Pachytene Pirnasmentioning

confidence: 99%

Section: Pachytene Pirnasmentioning

confidence: 99%

Chromatoid body and small RNAs in male germ cells

Meikar¹,

Ros²,

Korhonen³

et al. 2011

Reproduction

145

154

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“…Consistent with the involvement of Tudor domains, many such interactions were shown to depend on the presence of sDMAs on Piwi proteins. Both Piwi proteins and TDRDs are colocalized in several cytoplasmic perinuclear granules called the nuage, which are signature features of germ cells (Arkov and Ramos 2010). The TDRD proteins carry varying numbers of Tudor domains and are frequently associated with other domains that impart additional functions such as helicase activity or RNA binding (Handler et al 2011).…”

Section: Introductionmentioning

confidence: 99%

The multiple Tudor domain-containing protein TDRD1 is a molecular scaffold for mouse Piwi proteins and piRNA biogenesis factors

Mathioudakis

Palencia

Kadlec

et al. 2012

RNA

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Piwi-interacting RNAs (piRNAs) are small noncoding RNAs expressed in the germline of animals. They associate with Argonaute proteins of the Piwi subfamily, forming ribonucleoprotein complexes that are involved in maintaining genome integrity. The N-terminal region of some Piwi proteins contains symmetrically dimethylated arginines. This modification is thought to enable recruitment of Tudor domain-containing proteins (TDRDs), which might serve as platforms mediating interactions between various proteins in the piRNA pathway. We measured the binding affinity of the four individual extended Tudor domains (TDs) of murine TDRD1 protein for three different methylarginine-containing peptides from murine Piwi protein MILI. The results show a preference of TD2 and TD3 for consecutive MILI peptides, whereas TD4 and TD1 have, respectively, lower and very weak affinity for any peptide. The affinity of TD1 for methylarginine peptides can be restored by a single-point mutation back to the consensus aromatic cage sequence. These observations were confirmed by pull-down experiments with endogenous Piwi and Piwi-associated proteins. The crystal structure of TD3 bound to a methylated MILI peptide shows an unexpected orientation of the bound peptide, with additional contacts of nonmethylated residues being made outside of the aromatic cage, consistent with solution NMR titration experiments. Finally, the molecular envelope of the four tandem Tudor domains of TDRD1, derived from small angle scattering data, reveals a flexible, elongated shape for the protein. Overall, the results show that TDRD1 can accommodate different peptides from different proteins, and can therefore act as a scaffold protein for complex assembly in the piRNA pathway.

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“…Since their first discovery, at the end of the 19th century (Arkov & Ramos 2010), germ granules have delivered many of their secrets. EM, fluorescence imagery, and biochemical experiments have been particularly useful to describe the RNA and protein content of those cytoplasmic non-membranous and fibrous organelles, appreciate their diversity and dynamics, and understand their formation during germ cell differentiation.…”

Section: Concluding Remarks and Perspectivesmentioning

confidence: 99%

RNA-binding proteins, RNA granules, and gametes: is unity strength?

Nguyen-Chi¹,

Morello²

2011

Reproduction

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Changes in mRNA translation and degradation represent post-transcriptional processes operating during gametogenesis and early embryogenesis to ensure regulated protein synthesis. Numerous mRNA-binding proteins (RBPs) have been described in multiple animal models that contribute to the control of mRNA translation and decay during oogenesis and spermatogenesis. An emerging view from studies performed in germ cells and somatic cells is that RBPs associate with their target mRNAs in RNA-protein (or ribonucleoprotein) complexes (mRNPs) that assemble in various cytoplasmic RNA granules that communicate with the translation machinery and control mRNA storage, triage, and degradation. In comparison with Xenopus, Caenorhabditis elegans, or Drosophila, the composition and role of cytoplasmic RNA-containing granules in mammalian germ cells are still poorly understood. However, regained interest for these structures has emerged with the recent discovery of their role in small RNA synthesis and transposon silencing through DNA methylation. In this review, we will briefly summarize our current knowledge on cytoplasmic RNA granules in murine germ cells and describe the role of some of the RBPs they contain in regulating mRNA metabolism and small RNA processing during gametogenesis.

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Building RNA–protein granules: insight from the germline

Cited by 76 publications

References 112 publications

Chromatoid body and small RNAs in male germ cells

Chromatoid body and small RNAs in male germ cells

The multiple Tudor domain-containing protein TDRD1 is a molecular scaffold for mouse Piwi proteins and piRNA biogenesis factors

RNA-binding proteins, RNA granules, and gametes: is unity strength?

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