Not all lncMIRHGs are "junk transcripts,". LncM IRHG loci may make both functional miRNAs and lncRNAs, which can work together or separately

2021 ◽  
Author(s):  
Moataz Dowaidar

The human genome has various genomic regions that can create a large number of transcripts. RNAs that can function as both mRNA and noncoding RNA (lncRNA/snoRNA/miRNA) are known as bifunctional RNAs, or bifRNAs. BifRNAs have been detected in everything from microorganisms to humans. Cells may accurately modify the functions of the coding and noncoding regions of bifRNAs to satisfy relevant regulatory needs. However, it has not been thoroughly investigated whether the same gene locus may produce two types of functional nc transcripts, such as lncRNAs and miRNAs. These "bifunctional nc RNAs" are the topic of this review. This evaluation contained all the current information regarding LncMIRHGs. Some LINC MONOMER transcripts have not been proven to be "junk" according to this functional and mechanistic research. It is possible that the lncMIRHG locus makes both functional miRNAs and lncRNAs, some of which can act together and others of which may act independently. The data gathered via research by the NEAT1 organization also indicates that miRNA may function as a "pseudoRNA," with lncRNA produced from the lncMIRHG gene locus serving as the lead. A significant amount of focus on this class of lncRNAs must be given since the beauty of the lncMIRHG loci, which control these putative dual functions as lncRNA and miRNA, strongly recommends that we should do so. LincMIRHGs are utilized in a broad number of tasks, including those seen in disorders like cancer. It will be useful for medicine creation and development to have a full understanding of this lncRNA repertoire's mechanisms.

2016 ◽  
Author(s):  
Musaddeque Ahmed ◽  
Richard C. Sallari ◽  
Haiyang Guo ◽  
Jason H. Moore ◽  
Housheng Hansen He ◽  
...  

AbstractSummaryGenetic predispositions to diseases populate the noncoding regions of the human genome. Delineating their functional basis can inform on the mechanisms contributing to disease development. However, this remains a challenge due to the poor characterization of the noncoding genome. Variant Set Enrichment (VSE) is a fast method to calculate the enrichment of a set of disease-associated variants across functionally annotated genomic regions, consequently highlighting the mechanisms important in the etiology of the disease studied.Availability and ImplementationVSE is implemented as an R package and can easily be implemented in any system with R. See supplementary information for [email protected]; [email protected]


Genetics ◽  
1999 ◽  
Vol 152 (4) ◽  
pp. 1711-1722 ◽  
Author(s):  
Gavin A Huttley ◽  
Michael W Smith ◽  
Mary Carrington ◽  
Stephen J O’Brien

Abstract Linkage disequilibrium (LD), the tendency for alleles of linked loci to co-occur nonrandomly on chromosomal haplotypes, is an increasingly useful phenomenon for (1) revealing historic perturbation of populations including founder effects, admixture, or incomplete selective sweeps; (2) estimating elapsed time since such events based on time-dependent decay of LD; and (3) disease and phenotype mapping, particularly for traits not amenable to traditional pedigree analysis. Because few descriptions of LD for most regions of the human genome exist, we searched the human genome for the amount and extent of LD among 5048 autosomal short tandem repeat polymorphism (STRP) loci ascertained as specific haplotypes in the European CEPH mapping families. Evidence is presented indicating that ∼4% of STRP loci separated by <4.0 cM are in LD. The fraction of locus pairs within these intervals that display small Fisher’s exact test (FET) probabilities is directly proportional to the inverse of recombination distance between them (1/cM). The distribution of LD is nonuniform on a chromosomal scale and in a marker density-independent fashion, with chromosomes 2, 15, and 18 being significantly different from the genome average. Furthermore, a stepwise (locus-by-locus) 5-cM sliding-window analysis across 22 autosomes revealed nine genomic regions (2.2-6.4 cM), where the frequency of small FET probabilities among loci was greater than or equal to that presented by the HLA on chromosome 6, a region known to have extensive LD. Although the spatial heterogeneity of LD we detect in Europeans is consistent with the operation of natural selection, absence of a formal test for such genomic scale data prevents eliminating neutral processes as the evolutionary origin of the LD.


2020 ◽  
Author(s):  
Anyou Wang ◽  
Rong Hai

AbstractEukaryotic genomes gradually gain noncoding regions when advancing evolution and human genome actively transcribes >90% of its noncoding regions1, suggesting their criticality in evolutionary human genome. Yet <1% of them have been functionally characterized2, leaving most human genome in dark. Here we systematically decode endogenous lncRNAs located in unannotated regions of human genome and decipher a distinctive functional regime of lncRNAs hidden in massive RNAseq data. LncRNAs divergently distribute across chromosomes, independent of protein-coding regions. Their transcriptions barely initiate on promoters through polymerase II, but mostly on enhancers. Yet conventional enhancer activators(e.g. H3K4me1) only account for a small proportion of lncRNA activation, suggesting alternatively unknown mechanisms initiating the majority of lncRNAs. Meanwhile, lncRNA-self regulation also notably contributes to lncRNA activation. LncRNAs trans-regulate broad bioprocesses, including transcription and RNA processing, cell cycle, respiration, response to stress, chromatin organization, post-translational modification, and development. Overall lncRNAs govern their owned regime distinctive from protein’s.


ChemBioChem ◽  
2020 ◽  
Vol 21 (11) ◽  
pp. 1656-1663 ◽  
Author(s):  
Oliver Binas ◽  
Irene Bessi ◽  
Harald Schwalbe

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3644-3644
Author(s):  
Annalisa Di Ruscio ◽  
Alexander K Ebralidze ◽  
Francesco D'Alò ◽  
Maria Teresa Voso ◽  
Giuseppe Leone ◽  
...  

Abstract Abstract 3644 Poster Board III-580 Little is currently known about the role of noncoding RNA transcripts (ncRNA) in gene regulation; although most, and perhaps all, gene loci express such transcripts. Our previous results with the PU.1 gene locus showed a shared transcription factor complex and chromatin configuration requirements for biogenesis of both messenger and ncRNAs. These ncRNAs were localized within the nuclear and cytoplasmic compartments. Disrupting ncRNAs in the cytoplasmic cellular fraction results in increased PU.1 mRNA and protein. Recently, we have focused on the C/EBPa gene locus and observed extensive noncoding transcription. The transcription factor C/EBPa plays a pivotal role in hematopoietic stem cell (HSC) commitment and differentiation. Expression of the C/EBPa gene is tightly regulated during normal hematopoietic development, and dysregulation of C/EBPa expression can lead to lung cancer and leukemia. However, little is known about how the C/EBPa gene is regulated in vivo. In this study, we characterize ncRNAs derived from the C/EBPa locus and demonstrate their functional role in regulation of C/EBPa gene expression. First, northern blot analysis and RT PCR determined a predominantly nuclear localization of the C/EBPa ncRNAs. Second, strand-specific quantitative RT PCR demonstrated a concordant expression of coding and noncoding C/EBPa transcripts. Next, we investigated the results of ablation of ncRNAs using a lentiviral vector containing ncRNA-targeting shRNAs on the expression of the C/EBPa gene. We have observed that reduced levels of ncRNAs leads to a significant downregulation of the expression of coding messenger RNA. These data strongly suggest that C/EBPa ncRNAs play an important role in maintaining optimal expression of the C/EBPa gene at different stages of hematopoiesis and makes targeting noncoding transcripts a novel and attractive tool in correcting aberrant gene expression levels. Disclosures: No relevant conflicts of interest to declare.


Author(s):  
Graham A. W. Rook

As humans move from the natural environment in which we evolved into modern urban settings, there are striking increases in chronic inflammatory and psychiatric disorders. To understand and eventually take control of this phenomenon we have to understand how humans, and in particular our immune systems, evolved in partnership with microorganisms in the environment and in our own bodies. Humans are holobionts, composed of human cells containing the human genome passed on via the germline, but also a much larger number of microbial cells acquired from mother, family members, and the environment. This microbiota provides signals involved in the development of essentially all organ systems, including the brain, and provides data and signals that regulate metabolism and the immune system. The immune system evolved to perform the dual functions of managing this microbiota, while simultaneously protecting us from pathogens. By considering the evolution of the immune system and the ways in which lifestyle changes have altered our exposures to, and colonisation by microorganisms, we can identify the crucial factors leading to the modern urban pattern of disease.


2016 ◽  
Vol 113 (48) ◽  
pp. E7846-E7855 ◽  
Author(s):  
Halina Fedak ◽  
Malgorzata Palusinska ◽  
Katarzyna Krzyczmonik ◽  
Lien Brzezniak ◽  
Ruslan Yatusevich ◽  
...  

Seed dormancy is one of the most crucial process transitions in a plant’s life cycle. Its timing is tightly controlled by the expression level of the Delay of Germination 1 gene (DOG1).DOG1is the major quantitative trait locus for seed dormancy inArabidopsisand has been shown to control dormancy in many other plant species. This is reflected by the evolutionary conservation of the functional short alternatively polyadenylated form of theDOG1mRNA. Notably, the 3′ region ofDOG1, including the last exon that is not included in this transcript isoform, shows a high level of conservation at the DNA level, but the encoded polypeptide is poorly conserved. Here, we demonstrate that this region ofDOG1contains a promoter for the transcription of a noncoding antisense RNA,asDOG1, that is 5′ capped, polyadenylated, and relatively stable. This promoter is autonomous andasDOG1has an expression profile that is different from knownDOG1transcripts. Using several approaches we show thatasDOG1strongly suppressesDOG1expression during seed maturation incis, but is unable to do so intrans. Therefore, the negative regulation of seed dormancy byasDOG1incisresults in allele-specific suppression ofDOG1expression and promotes germination. Given the evolutionary conservation of theasDOG1promoter, we propose that thiscis-constrained noncoding RNA-mediated mechanism limiting the duration of seed dormancy functions across the Brassicaceae.


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