by Elizabeth Pennisi – Science Magazine Our 21,000 protein-coding genes aren’t the only readable units in our genome. At last More »
Misregulation of angiotensin II (Ang II) actions can lead to atherosclerosis and hypertension. Evaluating transcriptomic responses to Ang II in More »
from GenomeWeb NEW YORK (GenomeWeb News) – The National Human Genome Research Institute plans to launch a grant program that More »
by Elizabeth Pennisi – Science Magazine
Our 21,000 protein-coding genes aren’t the only readable units in our genome. At last count, another 13,000 “genes” specify mysterious molecules called long noncoding RNAs (lncRNAs), and when the final tallies are in, they may outnumber protein-coding genes. But what are these RNAs good for? Some researchers have suggested that they represent “noise”: DNA randomly converted to RNA that serves no purpose. Others propose that they may be as pivotal as proteins in guiding cellular processes. To find out, Jesse Engreitz, a graduate student working with Mitchell Guttman and Eric Lander at the Broad Institute in Cambridge, Massachusetts, has taken a close look at one of the first noncoding RNAs discovered, XIST, which was identified 20 years ago as a silencer that shuts down one of the X chromosomes in females to ensure the proper amount of gene activity.
Misregulation of angiotensin II (Ang II) actions can lead to atherosclerosis and hypertension. Evaluating transcriptomic responses to Ang II in vascular smooth muscle cells (VSMCs) is important to understand the gene networks regulated by Ang II which might uncover previously unidentified mechanisms and new therapeutic targets.
Researchers at the Beckman Research Institute of the City of Hope set out to identify all transcripts, including novel protein-coding and long non-coding RNAs, differentially expressed in response to Ang II in rat VSMCs using transcriptome and epigenome profiling.
De novo assembly of transcripts from RNA-seq revealed novel protein-coding and long non-coding RNAs (lncRNAs). The majority of the genomic loci of these novel transcripts are enriched for histone H3 lysine-4-trimethylation and histone H3 lysine-36-trimethylation, two chromatin modifications found at actively transcribed regions, providing further evidence that these are bonafide transcripts. Analysis of transcript abundance identified all protein-coding and lncRNAs regulated by Ang II. The researchers further discovered that one Ang II-regulated lncRNA functions as the host transcript for miR-221 and miR-222, two miRNAs implicated in cell proliferation. Additionally, siRNA-mediated knockdown of Lnc-Ang362 reduced proliferation of VSMCs.
These data provide novel insights into the epigenomic and transcriptomic effects of Ang II in VSMCs. They provide the first identification of Ang II-regulated lncRNAs, which suggests functional roles for these lncRNAs in mediating cellular responses to Ang II. Furthermore, the researchers identify one Ang II-regulated lncRNA that is responsible for the production of two miRNAs implicated in VSMC proliferation. These newly identified non-coding transcripts could be exploited as novel therapeutic targets for Ang II-associated cardiovascular diseases.
- Leung A, Trac C, Jin W, Lanting L, Akbany A, Sætrom P, Schones DE, Natarajan R. (2013) Novel Long Non-Coding RNAs Are Regulated by Angiotensin II in Vascular Smooth Muscle Cells. Circ Res [Epub ahead of print]. [abstract]
Long non-coding RNAs (lncRNAs) have been found to perform various functions in a wide variety of important biological processes. To make easier interpretation of lncRNA functionality and conduct deep mining on these transcribed sequences, it is convenient to classify lncRNAs into different groups. Here, researchers from the CAS Key Laboratory of Genome Sciences and Information, China summarize classification methods of lncRNAs according to their four major features, namely, genomic location and context, effect exerted on DNA sequences, mechanism of functioning and their targeting mechanism. In combination with the presently available function annotations, they explore potential relationships between different classification categories, and generalize and compare biological features of different lncRNAs within each category. Finally, they present our view on potential further studies. The researchers believe that the classifications of lncRNAs as indicated above are of fundamental importance for lncRNA studies, helpful for further investigation of specific lncRNAs, for formulation of new hypothesis based on different features of lncRNA and for exploration of the underlying lncRNA functional mechanisms.
Ma L, Bajic VB, Zhang Z. (2013) On the classification of long non-coding RNAs. RNA Biol 10(6). [article]
Myostatin, a member of the transforming growth factor-β (TGF-β) superfamily of secreted proteins, is a potent negative regulator of myogenesis. Free myostatin induces the phosphorylation of the Smad family of transcription factors, which, in turn, regulates gene expression, via the canonical TGF-β signaling pathway. There is, however, emerging evidence that myostatin can regulate gene expression independent of Smad signaling.
As such, researchers at the University of Calgary, Canada acquired global gene expression data from the gastrocnemius muscle of C57BL/6 mice following a 6-day treatment with recombinant myostatin compared with vehicle-treated animals. Of the many differentially expressed genes, the myostatin-associated decrease (-11.20-fold; P < 0.05) in the noncoding metastasis-associated lung adenocarcinoma transcript 1 (Malat1) was the most significant and the most intriguing because of numerous reports describing its novel role in regulating cell growth.
They therefore sought to further characterize the role of Malat1 expression in skeletal muscle myogenesis. RT-PCR-based quantification of C2C12 and primary human skeletal muscle cells revealed a significant and persistent upregulation (4- to 7-fold; P < 0.05) of Malat1 mRNA during the differentiation of myoblasts into myotubes. Conversely, targeted knockdown of Malat1 using siRNA suppressed myoblast proliferation by arresting cell growth in the G0/G1 phase. These results reveal Malat1 as novel downstream target of myostatin with a considerable ability to regulate myogenesis. The identification of new targets of myostatin will have important repercussions for regenerative biology through inhibition and/or reversal of muscle atrophy and wasting diseases.
- Watts R, Johnsen VL, Shearer J, Hittel DS. (2013) Myostatin-induced inhibition of the long noncoding RNA Malat1 is associated with decreased myogenesis. Am J Physiol Cell Physiol 304(10), C995-C1001. [abstract]
NEW YORK (GenomeWeb News) – The National Human Genome Research Institute plans to launch a grant program that would fund efforts to develop innovative computational approaches for interpreting variants found in the non-protein-coding regions of the human genome.
NHGRI’s advisory board yesterday approved the program, which will provide up to $500,000 per year to each of five or six projects to create new tools that will pare down the numbers of genomic variants that are thought to be contributing to diseases or other traits.
At its tri-annual meeting yesterday, the National Advisory Council for Human Genome Research agreed that the RFA program, “Interpreting Variation in Human Non-coding Genomic Regions Using Computational Approaches,” should proceed, and the plan now is for the first RFAs to be released in August…
Cells are highly organized structures. In addition to membrane delimited organelles, proteins and RNAs can organize themselves into specific domains. Some examples include stress granules and subnuclear bodies. This level of organization is essential for the correct execution of multiple processes in the cell, ranging from cell signaling to assembly of structures such as the ribosomes. Here the authors review evidence that noncoding RNAs play a critical role in the establishment and regulation of these domains. The unique abilities of RNA to mark the genome in a gene-specific and condition-specific manner and to serve as tethers nominate them as ideal molecular address codes.
Batista PJ, Chang HY. (2013) Cytotopic localization by long noncoding RNAs. Curr Opin Cell Biol 25(2), 195-9. [abstract]
|Post-Doc Fellow/Research Associate
Job Code: 76_195473
|POSTED: Apr 25|
|Employer:||Wayne State University||Type:||Full-time|
|Organization Type:||Higher Education Institution||Category:||Medical – Clinical|
Essential Functions: Assisting with transcriptional and post-transcriptional control of cell signaling in the immune system under physiological and pathological situations. Working with both human derived cells and stable cell line. Elucidate the role of microRNAs and other non-coding RNAs in immunity and integrate novel post-transcriptional circuits with well established signaling and transcriptional network.Other research duties as assigned.
Qualifications: Ph.D. in Immunology, Microbiology, Pathology, Biochemistry or related fields. Ability to design and execute experiments using conventional molecular biological techniques including analyzing RNA-seq and ChIP-seq data.Ability to work independently and critical thinking abilities. Outstanding communications skills both written and verbal.
About Wayne State University
Founded in 1868, Wayne State University is a nationally recognized metropolitan research institution offering more than 400 academic programs through 13 schools and colleges to nearly 32,000 students. Wayne State?s main campus in Midtown Detroit comprises 100 buildings over nearly 200 acres; its five extension centers offer higher education to people throughout Southeast Michigan. Wayne State is dedicated to preparing students to excel by combining the academic excellence of a major research university…(find out more…)
We have created a custom lncRNA expression array design (gencode.v15.lncrna.2probe.version1) with probes targeting the Gencode v15 human lncRNA annotation.
The design file is for the standard Agilent 8x60k expression array format, with two 60mer probes targeting each of 22,001 lncRNA transcripts.
The array also contains 17,535 catalogue probes targeting protein-coding genes. Similar arrays designed against an earlier version of Gencode lncRNA annotations were described in Derrien et al (Genome Res. 2012 Sep;22(9):1775-89).
We are making this design freely available to the scientific community – interested researchers may contact Rory Johnson for more information (firstname.lastname@example.org).
Because the design is a standard custom Agilent format, researchers can freely order microarray slides for their own projects, or else can employ hybridisation services such as that offered by the Centre for Genomic Regulation Genomics Core Facility.
While the role of small non-coding RNAs, such as miRNAs, in apoptosis control is well established, long non-coding RNAs (lncRNAs) have received less attention. Growth Arrest-Specific 5 (GAS5) encodes multiple snoRNAs within its introns, whilst exonic sequences produce lncRNA which can act as a riborepressor of the glucocorticoid and related receptors. GAS5 negatively regulates the survival of lymphoid and breast cells, and is aberrantly expressed in several cancers. Although cellular GAS5 levels decline as prostate cancer cells acquire castration-resistance, the influence of GAS5 on prostate cell survival has not been determined.
To address this question, researchers at Keele University, United Kingdom transfected prostate cell lines with GAS5-encoding plasmids or GAS5 siRNAs, and cell survival was assessed. Basal apoptosis increased, and cell survival decreased, after transfection of 22Rv1 cells with plasmids encoding GAS5 transcripts, including mature GAS5 lncRNA alone. Similar effects were observed in PC-3 cells. In stable clones of 22Rv1, cell death correlated strongly with cellular GAS5 levels. Induction of 22Rv1 cell death by UV-C irradiation and chemotherapeutic drugs was augmented in cells transiently transfected with GAS5 constructs, and attenuated following down-regulation of GAS5 expression. Again, in these experiments, cell death was strongly correlated with cellular GAS5 levels. Thus, GAS5 promotes the apoptosis of prostate cells, and exonic sequence, i.e. GAS5 lncRNA, is sufficient to mediate this activity. Abnormally low levels of GAS5 expression may therefore reduce the effectiveness of chemotherapeutic agents. Although several lncRNAs have recently been shown to control cell survival, this is the first report of a death-promoting lncRNA in prostate cells.
- Pickard MR, Mourtada-Maarabouni M, Williams GT. (2013) Long non-coding RNA GAS5 regulates apoptosis in prostate cancer cell lines. Biochim Biophys Acta [Epub ahead of print]. [abstract]