Birth and death of gene overlaps in vertebrates

<p>Abstract</p> <p>Background</p> <p>Between five and fourteen per cent of genes in the vertebrate genomes do overlap sharing some intronic and/or exonic sequence. It was observed that majority of these overlaps are not conserved among vertebrate lineages. Although several mechanisms have been proposed to explain gene overlap origination the evolutionary basis of these phenomenon are still not well understood. Here, we present results of the comparative analysis of several vertebrate genomes. The purpose of this study was to examine overlapping genes in the context of their evolution and mechanisms leading to their origin.</p> <p>Results</p> <p>Based on the presence and arrangement of human overlapping genes orthologs in rodent and fish genomes we developed 15 theoretical scenarios of overlapping genes evolution. Analysis of these theoretical scenarios and close examination of genomic sequences revealed new mechanisms leading to the overlaps evolution and confirmed that many of the vertebrate gene overlaps are not conserved. This study also demonstrates that repetitive elements contribute to the overlapping genes origination and, for the first time, that evolutionary events could lead to the loss of an ancient overlap.</p> <p>Conclusion</p> <p>Birth as well as most probably death of gene overlaps occurred over the entire time of vertebrate evolution and there wasn't any rapid origin or 'big bang' in the course of overlapping genes evolution. The major forces in the gene overlaps origination are transposition and exaptation. Our results also imply that origin of overlapping genes is not an issue of saving space and contracting genomes size.</p

miRNA in head and neck squamous cell carcinomas: promising but still distant future of personalized oncology

Head and neck squamous cell carcinoma is one of the most common and fatal cancers worldwide. Lack of appropriate preventive screening tests, late detection, and high heterogeneity of these tumors are the main reasons for the unsatisfactory effects of therapy and, consequently, unfavorable outcomes for patients. An opportunity to improve the quality of diagnostics and treatment of this group of cancers are microRNAs (miRNAs) — molecules with a great potential both as biomarkers and therapeutic targets. This review aims to present the characteristics of these short non-coding RNAs (ncRNAs) and summarize the current reports on their use in oncology focused on medical strategies tailored to patients’ needs

Identification of human tRNA:m(5)C methyltransferase catalysing intron-dependent m(5)C formation in the first position of the anticodon of the [Formula: see text]

We identified a human orthologue of tRNA:m(5)C methyltransferase from Saccharomyces cerevisiae, which has been previously shown to catalyse the specific modification of C(34) in the intron-containing yeast [Formula: see text]. Using transcripts of intron-less and intron-containing human [Formula: see text] genes as substrates, we have shown that m(5)C(34) is introduced only in the intron-containing tRNA precursors when the substrates were incubated in the HeLa extract. m(5)C(34) formation depends on the nucleotide sequence surrounding the wobble cytidine and on the structure of the prolongated anticodon stem. Expression of the human Trm4 (hTrm4) cDNA in yeast partially complements the lack of the endogenous Trm4p enzyme. The yeast extract prepared from the strain deprived of the endogenous TRM4 gene and transformed with hTrm4 cDNA exhibits the same activity and substrate specificity toward human pre-tRNA(Leu) transcripts as the HeLa extract. The hTrm4 MTase has a much narrower specificity against the yeast substrates than its yeast orthologue: human enzyme is not able to form m(5)C at positions 48 and 49 of human and yeast tRNA precursors. To our knowledge, this is the first report showing intron-dependent methylation of human [Formula: see text] and identification of human gene encoding tRNA methylase responsible for this reaction

Cancer, Retrogenes, and Evolution

This review summarizes the knowledge about retrogenes in the context of cancer and evolution. The retroposition, in which the processed mRNA from parental genes undergoes reverse transcription and the resulting cDNA is integrated back into the genome, results in additional copies of existing genes. Despite the initial misconception, retroposition-derived copies can become functional, and due to their role in the molecular evolution of genomes, they have been named the “seeds of evolution”. It is convincing that retrogenes, as important elements involved in the evolution of species, also take part in the evolution of neoplastic tumors at the cell and species levels. The occurrence of specific “resistance mechanisms” to neoplastic transformation in some species has been noted. This phenomenon has been related to additional gene copies, including retrogenes. In addition, the role of retrogenes in the evolution of tumors has been described. Retrogene expression correlates with the occurrence of specific cancer subtypes, their stages, and their response to therapy. Phylogenetic insights into retrogenes show that most cancer-related retrocopies arose in the lineage of primates, and the number of identified cancer-related retrogenes demonstrates that these duplicates are quite important players in human carcinogenesis

Biological functions of natural antisense transcripts

Natural antisense transcripts (NATs) are RNA molecules that originate from opposite DNA strands of the same genomic locus (cis-NAT) or unlinked genomic loci (trans-NAT). NATs may play various regulatory functions at the transcriptional level via transcriptional interference. NATs may also regulate gene expression levels post-transcriptionally via induction of epigenetic changes or double-stranded RNA formation, which may lead to endogenous RNA interference, RNA editing or RNA masking. The true biological significance of the natural antisense transcripts remains controversial despite many years of research. Here, we summarize the current state of knowledge and discuss the sense-antisense overlap regulatory mechanisms and their potential

lncRNA-RNA Interactions across the Human Transcriptome.

Long non-coding RNAs (lncRNAs) represent a numerous class of non-protein coding transcripts longer than 200 nucleotides. There is possibility that a fraction of lncRNAs are not functional and represent mere transcriptional noise but a growing body of evidence shows they are engaged in a plethora of molecular functions and contribute considerably to the observed diversification of eukaryotic transcriptomes and proteomes. Still, however, only ca. 1% of lncRNAs have well established functions and much remains to be done towards decipherment of their biological roles. One of the least studied aspects of lncRNAs biology is their engagement in gene expression regulation through RNA-RNA interactions. By hybridizing with mate RNA molecules, lncRNAs could potentially participate in modulation of pre-mRNA splicing, RNA editing, mRNA stability control, translation activation, or abrogation of miRNA-induced repression. Here, we implemented a similarity-search based method for transcriptome-wide identification of RNA-RNA interactions, which enabled us to find 18,871,097 lncRNA-RNA base-pairings in human. Further analyses showed that the interactions could be involved in processing, stability control and functions of 57,303 transcripts. An extensive use of RNA-Seq data provided support for approximately one third of the interactions, at least in terms of the two RNA components being co-expressed. The results suggest that lncRNA-RNA interactions are broadly used to regulate and diversify the human transcriptome

Gene structure evolution

With the growing number of sequenced genomes comparative studies of lineage specific genomic features become both very rewarding and challenging. Large scale multiple genomes analyses allow to decipher many genomic features. They show that main differences between related species concern not as much the number of genes or the presence of species specific genes as the differences in the gene structure organization. Although much has been learned about gene structure evolution many problems remain unsolved. Alternative splicing is one of the main mechanisms leading to the proteome diversification. The raise of new splice variants is strictly connected with the exon and intron loss and gain. Main mechanisms of how the new exons originate are known, but question which of them, if any, plays the main role remains open. Another unsolved mystery is the intron origination. The dispute between "intro-early" and "intron-late" hypotheses supporters leads us to many interesting findings but the problem remains unsolved. One of the most fascinating discoveries in the genome studies is the role of so called 'junk DNA' in the evolution of human and other vertebrates. Repetitive elements and retrogenes are one of the most important elements in the gene structure evolution. They provide signals, motifs and coding sequences for new exons, splice sites or regulatory elements. Another phenomenon discovered in the process of whole genomes analyses is the common presence of overlapping genes and, at the same time, their low conservation level