Protein synthesis and degradation are essential to regulate germline stem cell homeostasis in <i>Drosophila</i> testes

Yu, Jun; Xiang, Lan; Chen, Xia; Yu, Chao; Xu, Yiwen; Liu, Yujuan; Xu, Lingna; Fan, Heng‐Yu; Tong, Chao

doi:10.1242/dev.134247

Cited by 38 publications

(57 citation statements)

References 67 publications

(66 reference statements)

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“…This is exemplified by disruptions to the stem cell niche in the testis when RPs are knocked down e.g. RpL19 RNAi results in over-proliferation of early germ cells in D. melanogaster [21]. During the meiotic phase of gametogenesis, transcription does not occur [22]; therefore meiotic cells rely on post-transcriptional gene regulation [23].…”

Section: Introductionmentioning

confidence: 99%

Ribosome heterogeneity in Drosophila melanogaster gonads through paralog-switching

Aspden

Fontana

O’Connell

et al. 2020

Preprint

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13Ribosomes have long been thought of as homogeneous, macromolecular machines but 14 recent evidence suggests they are heterogeneous and their specialisation can regulate translation. 15Here, we have characterised ribosomal protein heterogeneity across 5 tissues of Drosophila 16 melanogaster. We find that testis and ovary contain the most heterogeneous ribosome populations, 17 and that specialisation in these tissues occurs through paralog-switching. For the first time, we have 18 solved structures of ribosomes purified from in vivo tissues by cryo-EM, revealing differences in 19 precise ribosomal arrangement for testis and ovary 80S ribosomes. Differences in the amino acid 20 composition of paralog pairs and their localisation on the ribosome exterior indicate paralog-21 switching could alter the ribosome surface, enabling different proteins to regulate translation. One 22 testis-specific paralog-switching pair is also found in humans, suggesting this is a conserved site of 23 ribosome specialisation. Overall, this work allows us to propose possible mechanisms by which 24 ribosome specialisation can regulate translation. 25 26 27 48 effects [1], whilst RpL38 mutants in D. melanogaster exhibit large wings, small bristles, delayed 49 development and disorganised wing hair polarity [14]. 50 2 Human cytoplasmic ribosomes usually comprise of 80 RPs and 4 rRNAs. This is similar across 51 the majority of multicellular eukaryotes including D. melanogaster with 80 RPs and 5 rRNAs. 52 However, annotated in FlyBase there are 93 cytoplasmic RP genes, including 39 small subunit 53 proteins and 54 large subunit proteins [15]. These additional genes code for 13 paralogs in D. 54 melanogaster. In fact, across eukaryotes many RP genes possess paralogs, for example human RpL3 55 and RpL3L [11] and Arabidopsis RpS8A and RpS8B [13]. In total, there are 19 pairs of paralogs in 56 humans [4] and all 80 RPs in Arabidopsis thaliana have paralogs [16].57 To dissect the function of ribosome heterogeneity it is necessary to understand biological 58 importance within context of whole organisms. Within the developmental biology field, a large 59 proportion of research focuses on the contribution of transcription to gene expression control.60 However, during development a variety of processes and key time points are highly dependent on 61 the regulation of mRNA translation (oogenesis in Xenopus [17], early embryo development in 62 Drosophila [18] and mammalian erythropoiesis [19]). The balance between self-renewal and 63 differentiation at the stem cell niche is highly dependent on translation in both the ovary and the 64 testis [20]. This is exemplified by disruptions to the stem cell niche in the testis when RPs are 65 knocked down e.g. RpL19 RNAi results in over-proliferation of early germ cells in D. melanogaster 66 [21]. During the meiotic phase of gametogenesis, transcription does not occur [22]; therefore 67 meiotic cells rely on post-transcriptional gene regulation [23]. The translational machinery has 68 evolved to become specialise...

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Section: Introductionmentioning

confidence: 99%

Ribosome heterogeneity in Drosophila melanogaster gonads through paralog-switching

Aspden

Fontana

O’Connell

et al. 2020

Preprint

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“…The stem cell niche is critically responsible for the selfrenewal and differentiation of GSCs, which mediate normal spermatogenesis (25); however, its molecular nature remains to be determined. This study revealed the function and mechanism of SmD3, which may act via RpL18 in the male stem cell niche of Drosophila.…”

Section: Discussionmentioning

confidence: 99%

“…The spliceosome and ribosome are important in the development of certain diseases (42,43). There is evidence that the spliceosome and ribosome are crucial for both GSC maintenance and early germ cell differentiation (25). In tj .SmD3 RNAi and tj .RpL18 RNAi testes, overproliferated germ cells led by differentiation defects accumulated, ultimately causing testicular germ cell tumors.…”

Section: Discussionmentioning

confidence: 99%

“…Nonetheless, the U2A component does not appear to play an essential role during the earlier stages of germ cell development, nor does it have a relevant function in the formation of cyst cells. In our previous study, Small ribonucleoprotein particle protein SmD3 (SmD3) was identified as a male GSC regulatory factor that functions in Drosophila testes (25). However, few reports have indicated the biologic function of SmD3 in human or animal models.…”

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Small ribonucleoprotein particle protein SmD3 governs the homeostasis of germline stem cells and the crosstalk between the spliceosome and ribosome signals in Drosophila

Luan

Yan

et al. 2019

FASEB j.

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The ribonucleoprotein (RNP) spliceosome machinery triggers the precursor RNA splicing process in eukaryotes. Major spliceosome defects are implicated in male infertility; however, the underlying mechanistic links between the spliceosome and the ribosome in Drosophila testes remains largely unresolved. Small ribonucleoprotein particle protein SmD3 (SmD3) is a novel germline stem cell (GSC) regulatory gene identified in our previous screen of Drosophila testes. In the present study, using genetic manipulation in a Drosophila model, we demonstrated that SmD3 is required for the GSC niche and controls the self‐renewal and differentiation of GSCs in the testis. Using in vitro assays in Schneider 2 cells, we showed that SmD3 also regulates the homeostasis of proliferation and apoptosis in Drosophila. Furthermore, using liquid chromatography–tandem mass spectrometry methods, SmD3 was identified as binding with ribosomal protein (Rp)L18, which is a key regulator of the large subunit in the ribosome. Moreover, SmD3 was observed to regulate spliceosome and ribosome subunit expression levels and controlled spliceosome and ribosome function via RpL18. Significantly, our findings revealed the genetic causes and molecular mechanisms underlying the stem cell niche and the crosstalk between the spliceosome and the ribosome.—Yu, J., Luan, X., Yan, Y., Qiao, C, Liu, Y., Zhao, D., Xie, B., Zheng, Q., Wang, M., Chen, W., Shen, C, He, Z., Hu, X., Huang, X., Li, H., Chen, B., Zheng, B., Chen, X., Fang, J. Small ribonucleoprotein particle protein SmD3 governs the homeostasis of germline stem cells and the crosstalk between the spliceosome and ribosome signals in Drosophila. FASEB J. 33, 8125–8137 (2019). http://www.fasebj.org

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“…Deletion of DDB1 in mice resulted in female infertility, increased rates of apoptosis and poor responses to ovulation signals (Yu et al, 2015). Moreover, DDB1 is also required for the maintenance of spermatogonial stem cells (SSCs) (Yu et al, 2016). Previously, we reported that Es-Cul4 might play an important role in regulating spermatogenesis (Wang et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

A core component of the CUL4 ubiquitin ligase complexes, DDB1, regulates spermatogenesis in the Chinese mitten crab, Eriocheir sinensis

Fang

Wang

et al. 2017

Gene

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Protein synthesis and degradation are essential to regulate germline stem cell homeostasis in Drosophila testes

Cited by 38 publications

References 67 publications

Ribosome heterogeneity in Drosophila melanogaster gonads through paralog-switching

Ribosome heterogeneity in Drosophila melanogaster gonads through paralog-switching

Small ribonucleoprotein particle protein SmD3 governs the homeostasis of germline stem cells and the crosstalk between the spliceosome and ribosome signals in Drosophila

A core component of the CUL4 ubiquitin ligase complexes, DDB1, regulates spermatogenesis in the Chinese mitten crab, Eriocheir sinensis

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