Conserved Regulation of Cardiac Calcium Uptake by Peptides Encoded in Small Open Reading Frames

Science ◽  
2013 ◽  
Vol 341 (6150) ◽  
pp. 1116-1120 ◽  
Author(s):  
Emile G. Magny ◽  
Jose Ignacio Pueyo ◽  
Frances M.G. Pearl ◽  
Miguel Angel Cespedes ◽  
Jeremy E. Niven ◽  
...  

Small open reading frames (smORFs) are short DNA sequences that are able to encode small peptides of less than 100 amino acids. Study of these elements has been neglected despite thousands existing in our genomes. We and others previously showed that peptides as short as 11 amino acids are translated and provide essential functions during insect development. Here, we describe two peptides of less than 30 amino acids regulating calcium transport, and hence influencing regular muscle contraction, in the Drosophila heart. These peptides seem conserved for more than 550 million years in a range of species from flies to humans, in which they have been implicated in cardiac pathologies. Such conservation suggests that the mechanisms for heart regulation are ancient and that smORFs may be a fundamental genome component that should be studied systematically.

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Julie L Aspden ◽  
Ying Chen Eyre-Walker ◽  
Rose J Phillips ◽  
Unum Amin ◽  
Muhammad Ali S Mumtaz ◽  
...  

Thousands of small Open Reading Frames (smORFs) with the potential to encode small peptides of fewer than 100 amino acids exist in our genomes. However, the number of smORFs actually translated, and their molecular and functional roles are still unclear. In this study, we present a genome-wide assessment of smORF translation by ribosomal profiling of polysomal fractions in Drosophila. We detect two types of smORFs bound by multiple ribosomes and thus undergoing productive translation. The ‘longer’ smORFs of around 80 amino acids resemble canonical proteins in translational metrics and conservation, and display a propensity to contain transmembrane motifs. The ‘dwarf’ smORFs are in general shorter (around 20 amino-acid long), are mostly found in 5′-UTRs and non-coding RNAs, are less well conserved, and have no bioinformatic indicators of peptide function. Our findings indicate that thousands of smORFs are translated in metazoan genomes, reinforcing the idea that smORFs are an abundant and fundamental genome component.


Genetics ◽  
1992 ◽  
Vol 132 (1) ◽  
pp. 75-85 ◽  
Author(s):  
Y Lin ◽  
K L Larson ◽  
R Dorer ◽  
G R Smith

Abstract The Schizosaccharomyces pombe rec7 and rec8 genes, which are required for meiotic intragenic recombination but not for mitotic recombination, have been cloned and their DNA sequences determined. Genetic and physical analyses demonstrated that the cloned fragments contained the rec genes rather than rec mutation suppressors. A 1.6-kb DNA fragment contained a functional rec7 gene, and a 2.1-kb fragment contained a functional rec8 gene. The nucleotide sequences of these fragments revealed open reading frames predicting 249 amino acids for the rec7 gene product and 393 amino acids for the rec8 gene product. Northern hybridization analysis showed that both rec gene mRNAs were detectable only at 2-3 hr after induction of meiosis. The absence of these mRNAs in mitosis and their disappearance at 4 hr and later in meiosis suggest that the rec7 and rec8 gene products may be involved primarily in the early steps of meiotic recombination in S. pombe.


Genetics ◽  
1994 ◽  
Vol 136 (3) ◽  
pp. 769-779 ◽  
Author(s):  
Y Lin ◽  
G R Smith

Abstract Two meiotic recombination genes, rec6 and rec12, from Schizosaccharomyces pombe have been cloned by genetic complementation and their DNA sequences determined. Gene replacements demonstrated that the cloned fragments contained the rec6 and rec12 genes. Further analysis showed that the functional rec6 gene was within a 1.3-kb fragment and rec12 within a 1.7-kb fragment. The nucleotide sequences of these fragments revealed open reading frames (ORFs) predicting 143 amino acids for the rec6 gene product and 139 amino acids for the rec12 gene product. After pat1-114 temperature-induced meiosis, the transcripts of rec6 and rec12 were induced to maximal levels at 2-3 hr, at about the time of premeiotic DNA synthesis, but were present at much lower levels before and after this time. The transient induction of the transcripts and the phenotypes of the mutants suggest that the rec6 and rec12 gene products are involved primarily in the early steps of meiotic recombination in S. pombe. Near the rec6 gene are two additional ORFs potentially encoding proteins with homology to ribosomal protein S7 of Saccharomyces cerevisiae (ORF137) and to the homeodomain of developmental regulatory proteins (ORF201). The roles of these S. pombe ORFs remain to be determined.


2019 ◽  
Vol 8 (43) ◽  
Author(s):  
T. O. C. Faleye ◽  
O. M. Adewumi ◽  
D. Klapsa ◽  
M. Majumdar ◽  
J. Martin ◽  
...  

Here, we describe nearly complete genome sequences (7,361 nucleotides [nt] and 6,893 nt) of two echovirus 20 (E20) isolates from Nigeria that were simultaneously typed as CVB and E20 (dual serotype) by neutralization assay. Both include two overlapping open reading frames (ORFs) of 67 and 2,183 amino acids that encoded a recently described gut infection-facilitating protein and the classic enterovirus proteins, respectively.


2020 ◽  
Author(s):  
Justin A. Bosch ◽  
Berrak Ugur ◽  
Israel Pichardo-Casas ◽  
Jorden Rabasco ◽  
Felipe Escobedo ◽  
...  

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.


2020 ◽  
Vol 6 (4) ◽  
pp. 41
Author(s):  
Mihnea P. Dragomir ◽  
Ganiraju C. Manyam ◽  
Leonie Florence Ott ◽  
Léa Berland ◽  
Erik Knutsen ◽  
...  

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.


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