Special Issue "The Value of Being Different: Ultraconserved Genomic Elements, Micro Peptides and Chimeric RNAs"

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: closed (30 November 2017).

Special Issue Editor

Dr. Teresa Colombo
Website
Guest Editor
Institute for Systems Analysis and Computer Science "Antonio Ruberti" (IASI), National Research Council (CNR), Rome, Italy
Interests: cancer biology; genomics; epigenomics; non-coding RNAs; high-throughput sequencing

Special Issue Information

Dear Colleagues,


Molecular biology is a fascinating, ever surprising field. The more sophisticated technology becomes, the more we are surprised by new features. Thousands of eukaryotic genomes have been sequenced, biomedical investigation has moved to the genome scale, and coordinated efforts of international consortia have deepened our understanding of the structure and functions of genomes, transcriptomes, and proteomes. However, invariably, our paradigms continue to be challenged, with unexpected discoveries behind each newly-opened door.


With this Special Issue ,we invite the readers on a journey through some of the most surprising oddities discovered in the last few decades regarding DNA, RNA, and proteins, such as ultra-conserved elements (UCEs) populating vertebrate genomes, chimeric RNAs with no genomic DNA basis, as well as functional micropeptides, about a hundred amino acids long, which challenge the idea of protein-coding and noncoding potentials.


As a side theme, all of these exciting discoveries were enabled by high-throughput sequencing (HTS) technologies. In fact, HTS made a wealth of sequenced genomes available, empowering comparative analyses in the discovery of the existence of chunks of genomes that stubbornly resist mutations. Similarly, application of HTS techniques to ribosome profiling has captured the translation potential in short open reading frames, previously deemed as noncoding, which fulfill essential roles in crucial biological. Finally, meticulous analysis of unmappable reads from RNA profiling experiments have unveiled a number of fusion transcripts, originating from trans-splicing events, regardless of chromosomal translocations and/or rearrangements.

Dr. Teresa Colombo
Guest Editor

Manuscript Submission Information

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Keywords


  • cancer genomics
  • epigenomics
  • non-coding RNAs
  • ultraconserved genomic elements
  • micropeptides
  • chimeric RNAs
  • high-throughput sequencing technologies


 

Published Papers (4 papers)

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Research

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Open AccessArticle
Absence of Correlation between Chimeric RNA and Aging
Genes 2017, 8(12), 386; https://doi.org/10.3390/genes8120386 - 14 Dec 2017
Cited by 4
Abstract
Chimeric RNAs have been recognized as a phenomenon not unique to cancer cells. They also exist in normal physiology. Aging is often characterized by deregulation of molecular and cellular mechanisms, including loss of heterochromatin, increased transcriptional noise, less tight control on alternative splicing, [...] Read more.
Chimeric RNAs have been recognized as a phenomenon not unique to cancer cells. They also exist in normal physiology. Aging is often characterized by deregulation of molecular and cellular mechanisms, including loss of heterochromatin, increased transcriptional noise, less tight control on alternative splicing, and more stress-induced changes. It is thus assumed that chimeric RNAs are more abundant in older people. In this study, we conducted a preliminary investigation to identify any chimeric RNAs with age-based trends in their expression levels in blood samples. A chimeric RNA candidate list generated by bioinformatic analysis indicated the possibility of both negative and positive trends in the expression of chimeric RNAs. Out of this candidate list, five novel chimeric RNAs were successfully amplified in multiple blood samples and then sequenced. Although primary smaller sample sizes displayed some weak trends with respect to age, analysis of quantitative PCR data from larger sample sizes showed essentially no relationship between expression levels and age. Altogether, these results indicate that, contradictory to the common assumption, chimeric RNAs as a group are not all higher in older individuals and that placing chimeric RNAs in the context of aging will be a much more complex task than initially anticipated. Full article
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Open AccessArticle
Connections between Transcription Downstream of Genes and cis-SAGe Chimeric RNA
Genes 2017, 8(11), 338; https://doi.org/10.3390/genes8110338 - 22 Nov 2017
Cited by 3
Abstract
cis-Splicing between adjacent genes (cis-SAGe) is being recognized as one way to produce chimeric fusion RNAs. However, its detail mechanism is not clear. Recent study revealed induction of transcriptions downstream of genes (DoGs) under osmotic stress. Here, we investigated the influence of osmotic [...] Read more.
cis-Splicing between adjacent genes (cis-SAGe) is being recognized as one way to produce chimeric fusion RNAs. However, its detail mechanism is not clear. Recent study revealed induction of transcriptions downstream of genes (DoGs) under osmotic stress. Here, we investigated the influence of osmotic stress on cis-SAGe chimeric RNAs and their connection to DoGs. We found, the absence of induction of at least some cis-SAGe fusions and/or their corresponding DoGs at early time point(s). In fact, these DoGs and their cis-SAGe fusions are inversely correlated. This negative correlation was changed to positive at a later time point. These results suggest a direct competition between the two categories of transcripts when total pool of readthrough transcripts is limited at an early time point. At a later time point, DoGs and corresponding cis-SAGe fusions are both induced, indicating that total readthrough transcripts become more abundant. Finally, we observed overall enhancement of cis-SAGe chimeric RNAs in KCl-treated samples by RNA-Seq analysis. Full article
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Open AccessArticle
Viral Infection Identifies Micropeptides Differentially Regulated in smORF-Containing lncRNAs
Genes 2017, 8(8), 206; https://doi.org/10.3390/genes8080206 - 21 Aug 2017
Cited by 17
Abstract
Viral infection leads to a robust cellular response whereby the infected cell produces hundreds of molecular regulators to combat infection. Currently, non-canonical components, e.g., long noncoding RNAs (lncRNAs) have been added to the repertoire of immune regulators involved in the antiviral program. Interestingly, [...] Read more.
Viral infection leads to a robust cellular response whereby the infected cell produces hundreds of molecular regulators to combat infection. Currently, non-canonical components, e.g., long noncoding RNAs (lncRNAs) have been added to the repertoire of immune regulators involved in the antiviral program. Interestingly, studies utilizing next-generation sequencing technologies show that a subset of the >10,000 lncRNAs in the mammalian genome contain small open reading frames (smORFs) associated with active translation, i.e., many lncRNAs are not noncoding. Here, we use genome-wide high-throughput methods to identify potential micropeptides in smORF-containing lncRNAs involved in the immune response. Using influenza as a viral infection model, we performed RNA-seq and ribosome profiling to track expression and translation of putative lncRNAs that may encode for peptides and identify tens of potential candidates. Interestingly, many of these peptides are highly conserved at the protein level, strongly suggesting biological relevance and activity. By perusing publicly available data sets, four potential peptides of interest seem common to stress induction and/or are highly conserved; potential peptides from the MMP24-AS1, ZFAS1, RP11-622K12.1, and MIR22HG genes. Interestingly, using an antibody against the potential peptide encoded by MIR22HG RNA, we show that the peptide is stably expressed in the absence of infection, and upregulated in response to infection, corroborating the prediction of the ribosome profiling results. These data show the utility of perturbation approaches in identifying potentially relevant novel molecules encoded in the genome. Full article
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Review

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Open AccessReview
Transcriptional-Readthrough RNAs Reflect the Phenomenon of “A Gene Contains Gene(s)” or “Gene(s) within a Gene” in the Human Genome, and Thus Are Not Chimeric RNAs
Genes 2018, 9(1), 40; https://doi.org/10.3390/genes9010040 - 16 Jan 2018
Cited by 13
Abstract
Tens of thousands of chimeric RNAs, i.e., RNAs with sequences of two genes, have been identified in human cells. Most of them are formed by two neighboring genes on the same chromosome and are considered to be derived via transcriptional readthrough, but a [...] Read more.
Tens of thousands of chimeric RNAs, i.e., RNAs with sequences of two genes, have been identified in human cells. Most of them are formed by two neighboring genes on the same chromosome and are considered to be derived via transcriptional readthrough, but a true readthrough event still awaits more evidence and trans-splicing that joins two transcripts together remains as a possible mechanism. We regard those genomic loci that are transcriptionally read through as unannotated genes, because their transcriptional and posttranscriptional regulations are the same as those of already-annotated genes, including fusion genes formed due to genetic alterations. Therefore, readthrough RNAs and fusion-gene-derived RNAs are not chimeras. Only those two-gene RNAs formed at the RNA level, likely via trans-splicing, without corresponding genes as genomic parents, should be regarded as authentic chimeric RNAs. However, since in human cells, procedural and mechanistic details of trans-splicing have never been disclosed, we doubt the existence of trans-splicing. Therefore, there are probably no authentic chimeras in humans, after readthrough and fusion-gene derived RNAs are all put back into the group of ordinary RNAs. Therefore, it should be further determined whether in human cells all two-neighboring-gene RNAs are derived from transcriptional readthrough and whether trans-splicing truly exists. Full article
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