The 2024 Nobel Prize in Physiology or Medicine: microRNA Takes Center Stage.

The Journal Editorial Board Members would like to congratulate Victor Ambros and Gary Ruvkun, who were jointly awarded the 2024 Nobel Prize in Physiology or Medicine for their groundbreaking discovery of microRNAs and the role of microRNAs in post-transcriptional gene regulation, uncovering a previously unknown layer of gene control in eukaryotes [...

Origin of functional de novo genes in humans from "hopeful monsters".

For a long time, it was believed that new genes arise only from modifications of preexisting genes, but the discovery of de novo protein-coding genes that originated from noncoding DNA regions demonstrates the existence of a "motherless" origination process for new genes. However, the features, distributions, expression profiles, and origin modes of these genes in humans seem to support the notion that their origin is not a purely "motherless" process; rather, these genes arise preferentially from genomic regions encoding preexisting precursors with gene-like features. In such a case, the gene loci are typically not brand new.

An ancestral genomic sequence that serves as a nucleation site for de novo gene birth.

The process of gene birth is of major interest with current excitement concerning de novo gene formation. We report a new and different mechanism of de novo gene birth based on the finding and the characteristics of a short non-coding sequence situated between two protein genes, termed a spacer sequence. This non-coding sequence is present in genomes of Mus musculus, the house mouse and Philippine tarsier, a primitive ancestral primate.

The Journal Club: Highlights on Recent Papers-10.

We are delighted to share with you our seventh Journal Club and highlight some of the most interesting papers published recently [...

Birth of a Regulatory Long Non-coding RNA/Gene, .

The origin of genes has been a major topic of research for many years, albeit in some cases, it has been a difficult process to elucidate. Insightful is a recent publication that experimentally shows how one gene, was born. This gene is regulated in a complex manner in male germ cells during spermatogenesis and is believed to participate in the regulation of levels of the ubiquitin specific peptidase 18 () mRNA.

Genesis of Non-Coding RNA Genes in Human Chromosome 22-A Sequence Connection with Protein Genes Separated by Evolutionary Time.

A small phylogenetically conserved sequence of 11,231 bp, termed FAM247, is repeated in human chromosome 22 by segmental duplications. This sequence forms part of diverse genes that span evolutionary time, the protein genes being the earliest as they are present in zebrafish and/or mice genomes, and the long noncoding RNA genes and pseudogenes the most recent as they appear to be present only in the human genome. We propose that the conserved sequence provides a nucleation site for new gene development at evolutionarily conserved chromosomal loci where the FAM247 sequences reside.

Formation of human long intergenic non-coding RNA genes, pseudogenes, and protein genes: Ancestral sequences are key players.

Pathways leading to formation of non-coding RNA and protein genes are varied and complex. We report finding a conserved repeat sequence present in human and chimpanzee genomes that appears to have originated from a common primate ancestor. This sequence is repeatedly copied in human chromosome 22 (chr22) low copy repeats (LCR22) or segmental duplications and forms twenty-one different genes, which include the human long intergenic non-coding RNA (lincRNA) family FAM230, a newly discovered lincRNA gene family termed conserved long intergenic non-coding RNAs (clincRNA), pseudogene families, as well as the gamma-glutamyltransferase (GGT) protein gene family and the RNA pseudogenes that originate from GGT sequences.

Formation of a Family of Long Intergenic Noncoding RNA Genes with an Embedded Translocation Breakpoint Motif in Human Chromosomal Low Copy Repeats of 22q11.2-Some Surprises and Questions.

A family of long intergenic noncoding RNA (lincRNA) genes, is formed via gene sequence duplication, specifically in human chromosomal low copy repeats (LCR) or segmental duplications. This is the first group of lincRNA genes known to be formed by segmental duplications and is consistent with current views of evolution and the creation of new genes via DNA low copy repeats. It appears to be an efficient way to form multiple lincRNA genes.

A family of long intergenic non-coding RNA genes in human chromosomal region 22q11.2 carry a DNA translocation breakpoint/AT-rich sequence.

FAM230C, a long intergenic non-coding RNA (lincRNA) gene in human chromosome 13 (chr13) is a member of lincRNA genes termed family with sequence similarity 230. An analysis using bioinformatics search tools and alignment programs was undertaken to determine properties of FAM230C and its related genes. Results reveal that the DNA translocation element, the Translocation Breakpoint Type A (TBTA) sequence, which consists of satellite DNA, Alu elements, and AT-rich sequences is embedded in the FAM230C gene.

Discovery and characterization of the first non-coding RNA that regulates gene expression, micF RNA: A historical perspective.

The first evidence that RNA can function as a regulator of gene expression came from experiments with prokaryotes in the 1980s. It was shown that Escherichia coli micF is an independent gene, has its own promoter, and encodes a small non-coding RNA that base pairs with and inhibits translation of a target messenger RNA in response to environmental stress conditions. The micF RNA was isolated, sequenced and shown to be a primary transcript.

Complexity of a small non-protein coding sequence in chromosomal region 22q11.2: presence of specialized DNA secondary structures and RNA exon/intron motifs.

Background: DiGeorge Syndrome is a genetic abnormality involving ~3 Mb deletion in human chromosome 22, termed 22q.11.2.

Editorial on the Special Issue: Regulation by non-coding RNAs.

This Special Issue of IJMS is devoted to regulation by non-coding RNAs and contains both original research and review articles. An attempt is made to provide an up-to-date analysis of this very fast moving field and cover regulatory roles of both microRNAs and long non-coding RNAs. Multifaceted functions of these RNAs in normal cellular processes, as well as in disease progression, are highlighted.

The intertwining of transposable elements and non-coding RNAs.

Growing evidence shows a close association of transposable elements (TE) with non-coding RNAs (ncRNA), and a significant number of small ncRNAs originate from TEs. Further, ncRNAs linked with TE sequences participate in a wide-range of regulatory functions. Alu elements in particular are critical players in gene regulation and molecular pathways.

Regulating the regulator: MicF RNA controls expression of the global regulator Lrp.

Studies on the regulatory RNA MicF in Enterobacteriaceae reveal a pivotal role in gene regulation. Multiple target gene mRNAs were identified and, importantly, MicF RNA regulates the expression of the global regulatory gene lrp (Holmqvist et al., 2012; Corcoran et al.

Impact of small repeat sequences on bacterial genome evolution.

Intergenic regions of prokaryotic genomes carry multiple copies of terminal inverted repeat (TIR) sequences, the nonautonomous miniature inverted-repeat transposable element (MITE). In addition, there are the repetitive extragenic palindromic (REP) sequences that fold into a small stem loop rich in G-C bonding. And the clustered regularly interspaced short palindromic repeats (CRISPRs) display similar small stem loops but are an integral part of a complex genetic element.

Stem loop sequences specific to transposable element IS605 are found linked to lipoprotein genes in Borrelia plasmids.

Background: Plasmids of Borrelia species are dynamic structures that contain a large number of repetitive genes, gene fragments, and gene fusions. In addition, the transposable element IS605/200 family, as well as degenerate forms of this IS element, are prevalent. In Helicobacter pylori, flanking regions of the IS605 transposase gene contain sequences that fold into identical small stem loops.

Intergenic regions of Borrelia plasmids contain phylogenetically conserved RNA secondary structure motifs.

Background: Borrelia species are unusual in that they contain a large number of linear and circular plasmids. Many of these plasmids have long intergenic regions. These regions have many fragmented genes, repeated sequences and appear to be in a state of flux, but they may serve as reservoirs for evolutionary change and/or maintain stable motifs such as small RNA genes.

Small mobile sequences in bacteria display diverse structure/function motifs.

Small repeat sequences in bacterial genomes, which represent non-autonomous mobile elements, have close similarities to archaeon and eukaryotic miniature inverted repeat transposable elements. These repeat elements are found in both intergenic and intragenic chromosomal regions, and contain an array of diverse motifs. These can include DNA sequences containing an integration host factor binding site and a proposed DNA methyltransferase recognition site, transcribed RNA secondary structural motifs, which are involved in mRNA regulation, and translated open reading frames found fused to other open reading frames.

Enterobacterial small mobile sequences carry open reading frames and are found intragenically--evolutionary implications for formation of new peptides.

Intergenic repeat units of 127-bp (RU-1) and 168-bp (RU-2), as well as a newly-found class of 103-bp (RU-3), represent small mobile sequences in enterobacterial genomes present in multiple intergenic regions. These repeat sequences display similarities to eukaryotic miniature inverted-repeat transposable elements (MITE). The RU mobile elements have not been reported to encode amino acid sequences.

Outer membrane protein genes and their small non-coding RNA regulator genes in Photorhabdus luminescens.

Introduction: Three major outer membrane protein genes of Escherichia coli, ompF, ompC, and ompA respond to stress factors. Transcripts from these genes are regulated by the small non-coding RNAs micF, micC, and micA, respectively. Here we examine Photorhabdus luminescens, an organism that has a different habitat from E.

Annotation and evolutionary relationships of a small regulatory RNA gene micF and its target ompF in Yersinia species.

Background: micF RNA, a small regulatory RNA found in bacteria, post-transcriptionally regulates expression of outer membrane protein F (OmpF) by interaction with the ompF mRNA 5'UTR. Phylogenetic data can be useful for RNA/RNA duplex structure analyses and aid in elucidation of mechanism of regulation. However micF and associated genes, ompF and ompC are difficult to annotate because of either similarities or divergences in nucleotide sequence.

MicF: an antisense RNA gene involved in response of Escherichia coli to global stress factors.

The micF gene is a stress response gene found in Escherichia coli and related bacteria that post-transcriptionally controls expression of the outer membrane porin gene ompF. The micF gene encodes a non-translated 93 nt antisense RNA that binds its target ompF mRNA and regulates ompF expression by inhibiting translation and inducing degradation of the message. In addition, other factors, such as the RNA chaperone protein StpA also play a role in this regulatory system.

Targeting the expression of anti-apoptotic proteins by antisense oligonucleotides.

Antisense oligonucleotide (ASO) biotechnology has been widely used to inhibit the expression of proteins involved in human disease. ASOs are designed to bind messenger RNA transcripts via Watson-Crick base-pairing and inhibit synthesis of targeted proteins. These proteins include protein kinases, growth factors, glutamate receptors, anti-apoptotic proteins, and proteins involved in genetic disorders.

Cleavage of mitochondria-like transfer RNAs expressed in Escherichia coli.

Mitochondrial (mt) transfer RNAs (tRNAs) often harbor unusual structural features causing their secondary structure to differ from the conventional cloverleaf. tRNAs designed with such irregularities, termed mt-like tRNAs, are active in Escherichia coli as suppressors of reporter genes, although they display low steady-state levels. Characterization of fragments produced during mt-like tRNA processing in vitro and in vivo suggests that these RNAs are not fully processed at their 5' ends and are cleaved internally.