Functional interplay between ribosomal protein paralogues in the e<i>RpL22</i> family in <i>Drosophila melanogaster</i>

Mageeney, Catherine M.; Kearse, Michael G.; Gershman, Brett W; Pritchard, Caroline E.; Colquhoun, Jennifer M.; Ware, Vassie C.

doi:10.1080/19336934.2018.1549419

Cited by 13 publications

(26 citation statements)

References 45 publications

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“…The function of the RpL22 and RpL22-like paralog pair in Drosophila testis has been explored and it has been suggested that the two proteins are not functionally redundant in development or spermatogenesis. However, knockdown of RpL22 is partially rescued by RpL22-like and vice versa [34, 35]. Further work is needed to directly link effects on ribosome composition and mRNA translational output, as the two paralogs may interact with different pools of mRNA in the testis [35].…”

Section: Discussionmentioning

confidence: 99%

Ribosome heterogeneity inDrosophila melanogastergonads 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: Discussionmentioning

confidence: 99%

Ribosome heterogeneity inDrosophila melanogastergonads through paralog-switching

Aspden

Fontana

O’Connell

et al. 2020

Preprint

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“…RPL22 paralogs represent an intriguing example of extra ribosomal function-gain and intergenic regulation throughout evolution. Extra ribosomal roles of Rpl22 paralogs were documented in yeast (see below), fruit fly, zebrafish, mice, and humans (Kearse et al, 2011;Mageeney et al, 2018;Zhang et al, 2017;O'Leary et al, 2013;Zhang et al, 2013). Human Rpl22 interacted with human telomerase RNA (Le et al, 2000) and was also sequestered, apparently in competition, by the Epstein-Barr virus (EBV)-encoded RNAs in EBV infected cells, possibly as part of the viral strategy to interfere with translation and growth (Fok, 2006;Houmani et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Regulation of yeast RPL22B splicing depends on intact pre-mRNA context of the intron

Abrhámová

Folk

2019

Preprint

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Yeast RPL22A and RPL22B genes form an intergenic regulatory loop modulating the ratio of paralogous transcripts in response to changing levels of proteins. Gabunilas and Chanfreau (Gabunilas and Chanfreau, PLoS Genet 12, e1005999, 2016) and our group (Abrhámová et al., PLoS ONE 13, e0190685, 2018) described that Rpl22 proteins bound to the divergent introns of RPL22 paralogs and inhibited splicing in dosage dependent manner.Here, we continued to study the splicing regulation in more detail and designed constructs for in vivo analyses of splicing efficiency. We also tested Rpl22 binding to RPL22B intron in three-hybrid system. We were able to confirm the findings reported originally by Gabunilas and Chanfreau on the importance of a stem loop structure within the RPL22B intron.Mutations which lowered the stability of the structure abolished Rpl22-mediated inhibition. In contrast, we were not able to confirm the sequence specificity with respect to either Rpl22 binding or splicing inhibition within this region, which they reported. We contradict their results that the 'RNA internal loop' of RPL22Bi (nt 178CCCU181 and 221UGAA224) is crucial for mediating the Rpl22 effects. We assume that this discrepancy reflects the difference in constructs, as the reporters used by Gabunilas and Chanfreau lacked the alternative 5' splice site as well as surrounding exons. Our own comparison confirms that deleting the sequence spanning alternative 5' splice site lowers splicing efficiency, hinting to possible disturbances of the regulatory mechanism. We argue that the structural context of the 'regulatory element' may reach across the intron or into the surrounding sequences, similarly to what was found previously for other genes, such as RPL30. Apparently, more detailed analyses are needed to discern this intriguing example of splicing regulation.

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“…We used the pair-rule gene, odd-skipped (Odd) to drive tissue-specific expression of an eRpL22-like.IR construct (previously developed by Mageeney et al 16 for expression of inverted repeats (IR) that form short hairpin RNA for eRpL22-like-specific knockdown) for RNAimediated depletion of eRpL22-like within the PE of the eye/antennal imaginal disc. Odd is expressed in margin F I G U R E 6 P-element mediated disruption of eRpL22-like diminishes eRpL22-like staining.…”

Section: In Vivo Erpl22-like Functional Depletion Studies Corroboramentioning

confidence: 99%

“…Whether or not paralogue-specific ribosomes within cells of the developing eye regulate translation of specific mRNAs is unknown, but this proposal should be considered in light of recent findings showing differential association of specific mRNAs on eRpL22-or eRpL22-like ribosomes in the male germline of Drosophila. 16 Thus, even within the ribosomal pool, eRpL22 and eRpL22-like may have distinctive roles in translation regulation. Alternatively, it is interesting to speculate that some eRpL22-like variants (particularly the high molecular mass species identified) may function outside of the ribosomal pathway in specific cells (as our IHC and Western blot data suggest) in apical regions of the PE and in the midpupal IoHC, reserving ribosomal functions for eRpL22 and the 34kD species of eRpL22-like.…”

Section: Unique Patterns Of Erpl22 and Erpl22-like Expression May Smentioning

confidence: 99%

“…In D melanogaster, the eRpL22 family includes two paralogues, eRpL22 and eRpL22-like -both essential in development. [14][15][16] eRpL22 is ubiquitously expressed [17][18][19][20] ; however, eRpL22-like shows tissue-specific expression in adult testes and the adult eye. 21 Tissue specificity in this Rp family may underlie specific roles for this paralogue in developing germ cells and in developing eye tissue.…”

Section: Introductionmentioning

confidence: 99%

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Tissue‐specific expression of ribosomal protein paralogue eRpL22‐like in Drosophila melanogaster eye development

Gershman

Pritchard

Chaney

et al. 2020

Developmental Dynamics

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Background Differences in core or tissue‐specific ribosomal protein (Rp) composition within ribosomes contribute to ribosome heterogeneity and functional variability. Yet, the degree to which ribosome heterogeneity modulates development is unknown. The Drosophila melanogaster eRpL22 family contains structurally diverse paralogues, eRpL22 and eRpL22‐like. Unlike ubiquitously expressed eRpL22, eRpL22‐like expression is tissue‐specific, notably within the male germline and the eye. We investigated expression within the developing eye to uncover tissue/cell types where specific paralogue roles might be defined. Results Immunohistochemistry analysis confirms ubiquitous eRpL22 expression throughout eye development. In larvae, eRpL22‐like is ubiquitously expressed, but highly enriched in the peripodial epithelium (PE). In early pupae, eRpL22‐like is broadly distributed in multiple cell types, but later, is primarily enriched in interommatidial hair cells (IoHC). Adult patterns include the ring of accessory cells around ommatidia. Adult retinae IoHC patterning phenotypes (shown by scanning electron microscopy) may be linked to RNAi‐mediated eRpL22‐like depletion within larval PE. Immunoblots and polysome profile analyses show multiple variants of eRpL22‐like across development, with the variant at the expected molecular mass co‐sedimenting with active ribosomes. Conclusion Our data reveal differential patterns of eRpL22‐like expression relative to eRpL22 and suggest a specific role for eRpL22‐like in developmental patterning of the eye.

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Functional interplay between ribosomal protein paralogues in the eRpL22 family in Drosophila melanogaster

Cited by 13 publications

References 45 publications

Ribosome heterogeneity inDrosophila melanogastergonads through paralog-switching

Ribosome heterogeneity inDrosophila melanogastergonads through paralog-switching

Regulation of yeast RPL22B splicing depends on intact pre-mRNA context of the intron

Tissue‐specific expression of ribosomal protein paralogue eRpL22‐like in Drosophila melanogaster eye development

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