Search Results for: mammalian genome transcript

Epigenetic coordination of embryonic heart transcription by dynamically regulated long noncoding RNAs


The role of noncoding RNAs in mammalian biology is of great interest, especially since the Encyclopedia of DNA Elements results were published. Many have studied microRNAs in the heart, but little is known about their larger cousins, long noncoding RNAs (lncRNAs). Here, researchers from the Washington University School of Medicine used genome-wide sequencing and improved bioinformatics to quantify lncRNA expression in mouse hearts, define a subset of cardiac-specific lncRNAs, and measure dynamic lncRNA regulation during the transition between embryo and adult, and in the adult heart after experimental pressure overload (a model resembling human hypertensive cardiomyopathy). They linked specific regulated lncRNAs to cardiac-expressed mRNAs that they target and, through network analyses, discovered a broader role of regulated cardiac lncRNAs as modulators of key cardiac transcriptional pathways.

  • Matkovich SJ, Edwards JR, Grossenheider TC, de Guzman Strong C, Dorn GW 2nd. (2014) Epigenetic coordination of embryonic heart transcription by dynamically regulated long noncoding RNAs. Proc Natl Acad Sci U S A 111(33):12264-9. [abstract]

Upcoming Seminar – Long noncoding RNA: transcription noise or biological modulator? A view from studies in embryonic stem cells

Dr. Xiaohua Shen, Associate Professor
Tsinghua University, Beijing, China
Wednesday, June 25, 2014 – 11:00am
CCBR Red Room
Pervasive transcription in mammalian genome produces thousands of long noncoding RNA (lncRNA) transcripts. It has been hypothesized that lncRNAs as versatile modulators regulate diverse aspects of biology. However, their biological significance remains skeptical due to healthy concerns of subtle phenotypic differences caused by technical variation of knockdown. Despite a clear need to completely inactivate lncRNA function, targeted deletion of lncRNAs is still lacking in culture. Here, we systematically deleted multiple lncRNA loci (up to 217 kb) in embryonic stem cells (ESCs) by CRISPR/Cas9 system. Homozygous deletion mutants could be generated with high efficiency (up to 19%) in a short period of time (< 2 weeks). We have further characterized a lncRNA located ~40 kb from an ultraconserved, developmentally regulated gene cluster. We propose this lncRNA functions in cis to regulate its neighboring gene transcription and in trans to orchestrate ESC differentiation. Despite of recent burst of interest in lncRNAs, our knowledge is still limited to a handful of them. Thousands of lncRNAs await for functional characterization. While focusing on biology of individual lncRNA genes, we have tried to categorize lncRNA and reveal their function in groups. I will talk about our recent progress on one lncRNA catalogue in regulating transcription and developmental processes.
Dr. Zhaolei Zhang, Associate Professor, The Donnelly Centre

Functional insights into the role of nuclear-retained long noncoding RNAs in gene expression control in mammalian cells


The mammalian genome harbors thousands of long noncoding RNA (lncRNA) genes. Recent studies have indicated the involvement of several of these lncRNAs in the regulation of gene expression. lncRNAs play crucial roles in various biological processes ranging from epigenetic gene regulation, transcriptional control, to post-transcriptional regulation. lncRNAs are localized in various subcellular compartments, and major proportion of these are retained in the cell nucleus and could be broadly classified as nuclear-retained lncRNAs (nrRNAs). Based on the identified functions, members of the nrRNAs execute diverse roles, including providing architectural support to the hierarchical subnuclear organization and influencing the recruitment of chromatin modifier factors to specific chromatin sites. In this review, the authors summarize the recently described roles of mammalian nrRNAs in controlling gene expression by influencing chromatin organization, transcription, pre-mRNA processing, nuclear organization, and their involvement in disease.

  • Singh DK, Prasanth KV. (2013) Functional insights into the role of nuclear-retained long noncoding RNAs in gene expression control in mammalian cells. Chromosome Res [Epub ahead of print]. [abstract]

Identification of novel transcripts and noncoding RNAs in bovine skin by RNA-Seq


Deep RNA sequencing (RNA-Seq) has opened a new horizon for understanding global gene expression. The functional annotation of non-model mammalian genomes including bovines is still poor compared to that of human and mouse. This particularly applies to tissues without direct significance for milk and meat production, like skin, in spite of its multifunctional relevance for the individual.

Here, researchers fromthe  Leibniz Institute for Farm Animal Biology, Germany performed a whole transcriptome analysis of pigmented and nonpigmented bovine skin to describe the comprehensive transcript catalogue of this tissue. A total of 39,577 unique primary skin transcripts were mapped to the bovine reference genome assembly. The majority of the transcripts were mapped to known transcriptional units (65%). In addition to the reannotation of known genes, a substantial number (10,884) of unknown transcripts (UTs) were discovered, which had not previously been annotated. The classification of UTs was based on the prediction of their coding potential and comparative sequence analysis, subsequently followed by meticulous manual curation. The classification analysis and experimental validation of selected UTs confirmed that RNA-Seq data can be used to amend the annotation of known genes by providing evidence for additional exons, untranslated regions or splice variants, by approving genes predicted in silico and by identifying novel bovine loci. A large group of UTs (4,848) was predicted to potentially represent long noncoding RNA (lncRNA). Predominantly, potential lncRNAs mapped in intergenic chromosome regions (4,365) and therefore, were classified as potential intergenic lncRNA. This analysis revealed that only about 6% of all UTs displayed interspecies conservation and discovered a variety of unknown transcripts without interspecies homology but specific expression in bovine skin.

The results of this study demonstrate a complex transcript pattern for bovine skin and suggest a possible functional relevance of novel transcripts, including lncRNA, in the modulation of pigmentation processes. The results also indicate that the comprehensive identification and annotation of unknown transcripts from whole transcriptome analysis using RNA-Seq data remains a tremendous future challenge.

  • Weikard R, Hadlich F, Kuehn C. (2013) Identification of novel transcripts and noncoding RNAs in bovine skin by deep next generation sequencing. BMC Genomics 14(1), 789. [abstract]

The vast, conserved mammalian lincRNome


Genome analysis of humans and other mammals reveals a surprisingly small number of protein-coding genes, only slightly over 20,000 (although the diversity of actual proteins is substantially augmented by alternative transcription and alternative splicing). Recent analysis of the mammalian genomes and transcriptomes, in particular, using the RNA-seq technology, shows that, in addition to protein-coding genes, mammalian genomes encode many long non-coding RNAs. For some of these transcripts, various regulatory functions have been demonstrated, but on the whole the repertoire of long non-coding RNAs remains poorly characterized. Researchers at NCBI, NIH compared the identified long intergenic non-coding (linc)RNAs from human and mouse, and employed a specially developed statistical technique to estimate the size and evolutionary conservation of the human and mouse lincRNomes. The estimates show that there are at least twice as many human and mouse lincRNAs than there are protein-coding genes. Moreover, about two third of the lincRNA genes appear to be conserved between human and mouse, implying thousands of conserved but still uncharacterized functions.

Managadze D, Lobkovsky AE, Wolf YI, Shabalina SA, Rogozin IB, et al. (2013) The Vast, Conserved Mammalian lincRNome. PLoS Comput Biol 9(2), e1002917. [article]