Small Open Reading Frames: How Important Are They for Molecular Evolution?

Guerra-Almeida, Diego; Fonseca, Rodrigo Nunes da

doi:10.3389/fgene.2020.574737

Cited by 16 publications

(10 citation statements)

References 47 publications

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“…This collective function that is mainly related to a process rather than to individual ORFs, precisely relies on the quantity and diversity of the reservoir of freely evolving sequences that can be translated by pervasive translation. In line with Guerra-Almeida and Nunes-da-Fonseca (2020) 5 these results call for revisiting the concept of function in the context of the emergence of novel coding products. The landscape and diversity of pervasive translation under stress conditions or in tissues associated with emergence of genetic novelty (e.g., testis or brain [73][74][75][76] ), therefore deserves to be carefully investigated.…”

Section: Discussionsupporting

confidence: 74%

“…In fact, noncoding regions can be seen as a reservoir of unselected sequences, hosting thousands of small Open Reading Frames (ORFs) that could give rise to novel products if translated [1][2][3][4][5][6] . Precisely, OMICS technologies have provided a huge amount of data revealing the "omnipresence" of biological noise which has turned out to result from the pervasivity of biological processes.…”

Section: Introductionmentioning

confidence: 99%

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The Ribosome Profiling landscape of yeast reveals a high diversity in pervasive translation

Papadopoulos

Arbes

Chevrollier

et al. 2023

Preprint

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Pervasive translation is a widespread phenomenon that plays an important role in de novo gene birth; however, its underlying mechanisms remain unclear. Based on multiple Ribosome Profiling (Ribo-Seq) datasets, we investigated the RiboSeq landscape of coding and noncoding regions of yeast. Therefore, we developed a representation framework which allows the visual representation and rational classification of the entire diversity of Ribo-Seq signals that could be observed in yeast. We show that if coding regions are restricted to specific areas of the Ribo-Seq landscape, noncoding regions are associated with a wide diversity of translation signals and, conversely, populate the entire yeast Ribo-Seq landscape. Specifically, we reveal that noncoding regions are associated with canonical translation signals, but also with non-canonical ones absent from coding regions, and which appear to be a hallmark of pervasive translation. Notably, we report thousands of translated noncoding ORFs among which, 251 led to detectable products with Mass Spectrometry while being characterized by a wide range of translation specificities. Overall, we show that pervasive translation is not random with noncoding ORF translation signals being consistent across Ribo-Seq experiments. Finally, we show that the translation signal of noncoding ORFs is not explained by features related to the emergence of function, but rather determined by the translation start codon and the codon distribution in their two alternative frames. Overall, our results enable us to propose a topology of the pervasive Ribo-Seq landscape of a species, and open the way to future comparative analyses of this translation landscape under different conditions.

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Section: Discussionsupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

The Ribosome Profiling landscape of yeast reveals a high diversity in pervasive translation

Papadopoulos

Arbes

Chevrollier

et al. 2023

Preprint

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“…Overall, our results demonstrate that the R. prolixus smORF-containing gene mlpt is essential for digestive physiology, moulting and T. cruzi metacyclogenesis during vector development. Since hundreds of genes containing smORFs are present in the insect genomes [13] and are insufficiently investigated subjects in the studies of evolution of new genes [35], our results open up new possibilities in the search for new targets for vector control.…”

Section: Resultsmentioning

confidence: 99%

“…It is currently known that hundreds of genes containing smORFs are present in insect genomes and may be evolutionary associated with the evolution of more complex genes and new cellular functions [40]. However, due to a plethora of technical difficulties, ranging from in silico prediction to the establishment of functional assays, the vast majority of these smORFs are still insufficiently investigated.…”

Section: Discussionmentioning

confidence: 99%

The smORF-containing genemille-pattesis required for moulting andTrypanosoma cruzimetacyclogenesis in the Chagas disease vectorRhodnius prolixus

Azevedo

Rodrigues

Alves

et al. 2020

Preprint

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SummaryChagas disease is estimated to affect 8 million people worldwide and is responsible for approximately 10,000 deaths in Latin America every year [1]. 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 [2]. Here, we show that the prototypic smORF-containing gene mille-pattes/polished-rice/tarsalless (mlpt/pri/tal) [3-6] 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.

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“…The ultimate evidence for the coding status of a transcript can only be provided by the demonstration of the protein product. Association with ribosomes and the presence of short ORFs are both now known to be only indicators of coding potential [ 28 ]. Further, certain transcripts may perform non-coding RNA functions and also give rise to small peptides or proteins [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

A Novel Cis-Regulatory lncRNA, Kalnc2, Downregulates Kalrn Protein-Coding Transcripts in Mouse Neuronal Cells

Pal

Chaubey

Tanwar

et al. 2023

ncRNA

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The KALRN gene encodes several multi-domain protein isoforms that localize to neuronal synapses, conferring the ability to grow and retract dendritic spines and shaping axonal outgrowth, dendrite morphology, and dendritic spine re-modeling. The KALRN genomic locus is implicated in several neurodevelopmental and neuropsychiatric diseases, including autism, schizophrenia, bipolar disease, and intellectual disability. We have previously shown that a novel brain-specific long non-coding RNA (lncRNA) arising from the 5′ end of the kalrna gene, called durga, regulates neuronal morphology in zebrafish. Here, we characterized mammalian Kalrn loci, annotating and experimentally validating multiple novel non-coding RNAs, including linear and circular variants. Comparing the mouse and human loci, we show that certain non-coding RNAs and Kalrn protein-coding isoforms arising from the locus show similar expression dynamics during development. In humans, mice, and zebrafish, the 5′ end of the Kalrn locus gives rise to a chromatin-associated lncRNA that is present in adult ovaries, besides being expressed during brain development and enriched in certain regions of the adult brain. Ectopic expression of this lncRNA led to the downregulation of all the major Kalrn mRNA isoforms. We propose that this lncRNA arising from the 5′ end of the Kalrn locus is functionally the mammalian ortholog of zebrafish lncRNA durga.

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Small Open Reading Frames: How Important Are They for Molecular Evolution?

Cited by 16 publications

References 47 publications

The Ribosome Profiling landscape of yeast reveals a high diversity in pervasive translation

The Ribosome Profiling landscape of yeast reveals a high diversity in pervasive translation

The smORF-containing genemille-pattesis required for moulting andTrypanosoma cruzimetacyclogenesis in the Chagas disease vectorRhodnius prolixus

A Novel Cis-Regulatory lncRNA, Kalnc2, Downregulates Kalrn Protein-Coding Transcripts in Mouse Neuronal Cells

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