scholarly journals The mlpt/Ubr3/Svb module comprises an ancient developmental switch for embryonic patterning

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Suparna Ray ◽  
Miriam I Rosenberg ◽  
Hélène Chanut-Delalande ◽  
Amélie Decaras ◽  
Barbara Schwertner ◽  
...  
Keyword(s):  
Molecular Complexes ◽  
Open Reading Frames ◽  
Epidermal Differentiation ◽  
Editorial Note ◽  
Embryonic Patterning ◽  
Embryo Patterning ◽  
Polished Rice ◽  
Developmental Switch ◽  
Small Open Reading Frames ◽  
Drosophila Embryos

Small open reading frames (smORFs) encoding ‘micropeptides’ exhibit remarkable evolutionary complexity. Conserved peptides encoded by mille-pattes (mlpt)/polished rice (pri)/tarsal less (tal) are essential for embryo segmentation in Tribolium but, in Drosophila, function in terminal epidermal differentiation and patterning of adult legs. Here, we show that a molecular complex identified in Drosophila epidermal differentiation, comprising Mlpt peptides, ubiquitin-ligase Ubr3 and transcription factor Shavenbaby (Svb), represents an ancient developmental module required for early insect embryo patterning. We find that loss of segmentation function for this module in flies evolved concomitantly with restriction of Svb expression in early Drosophila embryos. Consistent with this observation, artificially restoring early Svb expression in flies causes segmentation defects that depend on mlpt function, demonstrating enduring potency of an ancestral developmental switch despite evolving embryonic patterning modes. These results highlight the evolutionary plasticity of conserved molecular complexes under the constraints of essential genetic networks.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).

scholarly journals millepattes micropeptides are an ancient developmental switch required for embryonic patterning

2018 ◽  
Author(s):  
Suparna Ray ◽  
Miriam I Rosenberg ◽  
Hélène Chanut-Delalande ◽  
Amelie Decaras ◽  
Barbara Schwertner ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Early Embryo ◽  
Open Reading Frames ◽  
Embryonic Patterning ◽  
Embryo Patterning ◽  
Ancestral Function ◽  
Small Orfs ◽  
Developmental Switch ◽  
Reading Frames ◽  
Small Open Reading Frames

SummarySmall open reading frames (smORFs) that code for “micropeptides” (10-100 amino acids) exhibit remarkable evolutionary complexity. Conserved micropeptides encoded by the millepattes (mlpt) gene are essential in Tribolium for embryogenesis but in Drosophila, function only in leg and cuticle differentiation. We find that a module identified in Drosophila trichome patterning, comprising Mlpt, UBR3, and Shaven-baby (Svb), coordinates early embryo patterning in several insect orders. Intriguingly, Mlpt segmentation function can be re-awakened in the Drosophila blastoderm, demonstrating the potency of an ancestral developmental switch retained despite evolving embryonic patterning modes. smORFs like millepattes thus illustrate plasticity of micropeptide functions despite constraints of essential genetic networks.One sentence summaryA module comprising the small ORFs mlpt/pri/tal, the transcription factor Svb, and the ubiquitin ligase UBR3, possesses an ancestral function in insect embryo patterning which is lost in flies but reactivated when Svb expression is restored.

scholarly journals The smORF-containing gene mille-pattes is required for moulting and Trypanosoma cruzi metacyclogenesis in the Chagas disease vector Rhodnius prolixus

2020 ◽  
Author(s):  
Carina Azevedo ◽  
Bruno Rodrigues ◽  
Sandy Alves ◽  
Lupis Ribeiro ◽  
Carlos Logullo ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Disease Transmission ◽  
Postembryonic Development ◽  
Rhodnius Prolixus ◽  
Open Reading Frames ◽  
Disease Spread ◽  
Polished Rice ◽  
Triatomine Bugs ◽  
Small Open Reading Frames

SummaryChagas disease is estimated to affect 8 million people worldwide and is responsible for approximately 10,000 deaths in Latin America every year. Control of the triatomine bugs that transmit the flagellated parasite Trypanosoma cruzi has been the most successful strategy to avoid disease spread. Genes containing small open reading frames (smORFs, < 100 amino acids) constitute a putative reservoir of new vector control targets, since hundreds of these genes are present in insect genomes. Here, we show that the prototypic smORF-containing gene mille-pattes/polished-rice/tarsalless (mlpt/pri/tal) is essential for postembryonic development of the kissing bug Rhodnius prolixus and for T. cruzi metacyclogenesis during the nymphal stages. Injection of double-stranded RNA against mlpt (Rp-dsmlpt) during the nymphal stages leads to a plethora of phenotypes, which impair postembryonic development. First, fourth or fifth stage nymphs injected with Rp-dsmlpt do not moult even in the presence of the ecdysone receptor (EcR) mRNA. Second, Rp-dsmlpt nymphs have defects in gut morphology, delayed haemoglobin digestion, and decreased defecation volume compared with those of the control nymphs. Third, Rp-mlpt knockdown inhibits T. cruzi differentiation to the trypomastigote infective stage (metacyclogenesis) inside the R. prolixus gut. Overall, our study is the first to provide evidence that a smORF-containing gene regulates vector physiology and parasitic cycle thus enabling the development of novel molecular strategies to eliminate Chagas disease transmission.

CLAMP regulates Zygotic Genome Activation in Drosophila embryos

Genetics ◽  
2021 ◽  
Author(s):  
Megan M Colonnetta ◽  
Juan E Abrahante ◽  
Paul Schedl ◽  
Daryl M Gohl ◽  
Girish Deshpande
Keyword(s):  
Temporal Dynamics ◽  
Embryonic Patterning ◽  
Zygotic Genome Activation ◽  
Promoter Sequences ◽  
Genome Wide ◽  
Zygotic Transcription ◽  
Pioneer Factor ◽  
Genome Activation ◽  
Drosophila Embryos ◽  
Zygotic Genome

Abstract Embryonic patterning is critically dependent on zygotic genome activation (ZGA). In Drosophila melanogaster embryos, the pioneer factor Zelda directs ZGA, possibly in conjunction with other factors. Here we have explored novel involvement of Chromatin-Linked Adapter for MSL Proteins (CLAMP) during ZGA. CLAMP binds thousands of sites genome-wide throughout early embryogenesis. Interestingly, CLAMP relocates to target promoter sequences across the genome when ZGA is initiated. Although there is a considerable overlap between CLAMP and Zelda binding sites, the proteins display distinct temporal dynamics. To assess whether CLAMP occupancy affects gene expression, we analyzed transcriptomes of embryos zygotically compromised for either clamp or zelda and found that transcript levels of many zygotically-activated genes are similarly affected. Importantly, compromising either clamp or zelda disrupted the expression of critical segmentation and sex determination genes bound by CLAMP (and Zelda). Furthermore, clamp knockdown embryos recapitulate other phenotypes observed in Zelda-depleted embryos, including nuclear division defects, centrosome aberrations, and a disorganized actomyosin network. Based on these data, we propose that CLAMP acts in concert with Zelda to regulate early zygotic transcription.

scholarly journals An Improved Human smORF Annnotation Workflow Combining De Novo Transcriptome Assembly and Ribo-Seq

2019 ◽  
Author(s):  
Thomas F. Martinez ◽  
Qian Chu ◽  
Cynthia Donaldson ◽  
Dan Tan ◽  
Maxim N. Shokhirev ◽  
...  
Keyword(s):  
De Novo ◽  
Transcriptome Assembly ◽  
Human Leukocyte ◽  
Open Reading Frames ◽  
Translation Efficiency ◽  
Proteomics Data ◽  
Protein Coding ◽  
Leukocyte Antigen ◽  
Human Genes ◽  
Small Open Reading Frames

Protein-coding small open reading frames (smORFs) are emerging as an important class of genes, however, the coding capacity of smORFs in the human genome is unclear. By integrating de novo transcriptome assembly and Ribo-Seq, we confidently annotate thousands of novel translated smORFs in three human cell lines. We find that smORF translation prediction is noisier than for annotated coding sequences, underscoring the importance of analyzing multiple experiments and footprinting conditions. These smORFs are located within non-coding and antisense transcripts, the UTRs of mRNAs, and unannotated transcripts. Analysis of RNA levels and translation efficiency during cellular stress identifies regulated smORFs, providing an approach to select smORFs for further investigation. Sequence conservation and signatures of positive selection indicate that encoded microproteins are likely functional. Additionally, proteomics data from enriched human leukocyte antigen complexes validates the translation of hundreds of smORFs and positions them as a source of novel antigens. Thus, smORFs represent a significant number of important, yet unexplored human genes.

scholarly journals Two neuronal peptides encoded from a single transcript regulate mitochondrial function in Drosophila

2020 ◽  
Author(s):  
Justin A. Bosch ◽  
Berrak Ugur ◽  
Israel Pichardo-Casas ◽  
Jorden Rabasco ◽  
Felipe Escobedo ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Double Mutant ◽  
Open Reading Frames ◽  
Biological Functions ◽  
Neuronal Function ◽  
Phenotypic Analysis ◽  
Single Transcript ◽  
Sequence Similarities ◽  
Reading Frames ◽  
Small Open Reading Frames

SummaryNaturally produced peptides (<100 amino acids) are important regulators of physiology, development, and metabolism. Recent studies have predicted that thousands of peptides may be translated from transcripts containing small open reading frames (smORFs). Here, we describe two previously uncharacterized peptides in Drosophila encoded by conserved smORFs, Sloth1 and Sloth2. These peptides are translated from the same bicistronic transcript and share sequence similarities, suggesting that they encode paralogs. We provide evidence that Sloth1/2 are highly expressed in neurons, localize to mitochondria, and form a complex. Double mutant analysis in animals and cell culture revealed that sloth1 and sloth2 are not functionally redundant, and their loss causes animal lethality, reduced neuronal function, impaired mitochondrial function, and neurodegeneration. These results suggest that phenotypic analysis of smORF genes in Drosophila can provide a wealth of information on the biological functions of this poorly characterized class of genes.

scholarly journals FuncPEP: A Database of Functional Peptides Encoded by Non-Coding RNAs

2020 ◽  
Vol 6 (4) ◽  
pp. 41
Author(s):  
Mihnea P. Dragomir ◽  
Ganiraju C. Manyam ◽  
Leonie Florence Ott ◽  
Léa Berland ◽  
Erik Knutsen ◽  
...  
Keyword(s):  
Open Reading Frames ◽  
Start Codon ◽  
Small Peptides ◽  
Reading Frame ◽  
Cellular Processes ◽  
New Class ◽  
Web Resource ◽  
Non Coding Rnas ◽  
Functional Peptides ◽  
Small Open Reading Frames

Non-coding RNAs (ncRNAs) are essential players in many cellular processes, from normal development to oncogenic transformation. Initially, ncRNAs were defined as transcripts that lacked an open reading frame (ORF). However, multiple lines of evidence suggest that certain ncRNAs encode small peptides of less than 100 amino acids. The sequences encoding these peptides are known as small open reading frames (smORFs), many initiating with the traditional AUG start codon but terminating with atypical stop codons, suggesting a different biogenesis. The ncRNA-encoded peptides (ncPEPs) are gradually becoming appreciated as a new class of functional molecules that contribute to diverse cellular processes, and are deregulated in different diseases contributing to pathogenesis. As multiple publications have identified unique ncPEPs, we appreciated the need for assembling a new web resource that could gather information about these functional ncPEPs. We developed FuncPEP, a new database of functional ncRNA encoded peptides, containing all experimentally validated and functionally characterized ncPEPs. Currently, FuncPEP includes a comprehensive annotation of 112 functional ncPEPs and specific details regarding the ncRNA transcripts that encode these peptides. We believe that FuncPEP will serve as a platform for further deciphering the biologic significance and medical use of ncPEPs. The link for FuncPEP database can be found at the end of the Introduction Section.

scholarly journals Hundreds of putatively functional small open reading frames in Drosophila

2011 ◽  
Vol 12 (11) ◽  
pp. R118 ◽  
Author(s):  
Emmanuel Ladoukakis ◽  
Vini Pereira ◽  
Emile G Magny ◽  
Adam Eyre-Walker ◽  
Juan Couso
Keyword(s):  
Open Reading Frames ◽  
Reading Frames ◽  
Small Open Reading Frames
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