Search Results for: incrna
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. Alu sequences embedded in both long non-coding RNAs (lncRNA) and mRNAs form the basis of targeted mRNA decay via short imperfect base-pairing. Imperfect pairing is prominent in most ncRNA/target RNA interactions and found throughout all biological kingdoms. The piRNA-Piwi complex is multifunctional, but plays a major role in protection against invasion by transposons. This is an RNA-based genetic immune system similar to the one found in prokaryotes, the CRISPR system. Thousands of long intergenic non-coding RNAs (lincRNAs) are associated with endogenous retrovirus LTR transposable elements in human cells. These TEs can provide regulatory signals for lincRNA genes. A surprisingly large number of long circular ncRNAs have been discovered in human fibroblasts. These serve as “sponges” for miRNAs. Alu sequences, encoded in introns that flank exons are proposed to participate in RNA circularization via Alu/Alu base-pairing. Diseases are increasingly found to have a TE/ncRNA etiology. A single point mutation in a SINE/Alu sequence in a human long non-coding RNA leads to brainstem atrophy and death. On the other hand, genomic clusters of repeat sequences as well as lncRNAs function in epigenetic regulation. Some clusters are unstable, which can lead to formation of diseases such as facioscapulohumeral muscular dystrophy. The future may hold more surprises regarding diseases associated with ncRNAs andTEs.
- Hadjiargyrou M, Delihas N. (2013) The Intertwining of Transposable Elements and Non-Coding RNAs. Int J Mol Sci 14(7), 13307-28. [article]
from Zone in With Zon
A Short Walk in the Wondrous, Wacky World of Long—and now Circular—Noncoding RNAs
I’m pleased by how much I learn when researching topics for new content, and this was certainly the case for long noncoding RNA (lncRNA), which was briefly mentioned in my last blog post, “Ripples from the 2013 TIDES Conference.” The topic piqued my interest so I set out to find out more. Plowing through lncRNA (aka lincRNA = large intergenic non-coding RNA) literature I quickly realized that there was an enormous amount of information, and the big challenge would be to capture some intriguing aspects without getting bogged down in “technical weeds” or being overly simplistic. In what follows there is a super brief introduction to what lncRNAs are and what they do—the latter is controversial—along with an appreciation for why lncRNAs are indeed a structurally and functionally wondrous class of nucleic acids that now encompass circular molecules. Maybe—to borrow from Forrest Gump—lncRNAs are like “a box of chocolates” for molecular biologists.
Incoming search terms:
The tumor microenvironment is a crucial determinant in tumor progression. Interstitial extracellular matrix (ECM), such as type I collagen (Col-1), is aberrantly enriched in the tumor microenvironment and promotes tumor progression. Long intergenic non-coding RNAs (lincRNA) are a new family of regulatory RNAs that modulate fundamental cellular processes via diverse mechanisms.
Researchers at Tulane University School of Medicine investigated whether the expression of lincRNAs was regulated by the tumor promoting Col-1. In a three-dimensional organotypic culture model using the reconstituted basement membrane ECM Matrigel (rBM 3-D), supplementation of Col-1 disrupted acini, a differentiation feature of well-differentiated lung adenocarcinoma cells, and concurrently induced the expression of a tumor-promoting lincRNA, HOX transcript antisense RNA (HOTAIR). Induction of HOTAIR by Col-1 was diminished by a neutralizing antibody against the Col-1 receptor alpha2beta1 integrin. Col-1 activates the expression of a reporter gene controlled by the human HOTAIR promoter. Moreover the expression of HOTAIR and Col-1 was concurrently up-regulated in human non-small cell lung cancer.
These findings indicate that tumor-promoting Col-1 up-regulates the expression of HOTAIR in NSCLC cells. These initial results warrant further investigation of HOTAIR and other lincRNA genes in lung tumorigenesis.
- Zhuang Y, Wang X, Nguyen HT, Zhuo Y, Cui X, Fewell C, Flemington EK, Shan B. (2013) Induction of long intergenic non-coding RNA HOTAIR in lung cancer cells by type I collagen. J Hematol Oncol 6(1), 35. [Epub ahead of print]. [article]
HOXA cluster antisense RNA 2 (HOXA-AS2) is a long non-coding RNA located between the HOXA3 and HOXA4 genes in the HOXA cluster. Its transcript is expressed in NB4 promyelocytic leukemia cells and human peripheral blood neutrophils, and expression is increased in NB4 cells treated with all trans retinoic acid (ATRA). Knockdown of HOXA-AS2 expression by transduced shRNA decreases the number of viable cells and increases the proportion of apoptotic cells, measured by annexin V binding and by activity and cleavage of caspases-3, -8, and -9. The increase in death of HOXA-AS2 knockdown cells was accompanied by an elevated TNF-related apoptosis-inducing ligand (TRAIL) levels, but ATRA-induced NB4 cells treated with TRAIL did show an increase in HOXA-AS2 expression. These results demonstrate that ATRA induction of HOXA-AS2 suppresses ATRA-induced apoptosis, possibly through a TRAIL-mediated pathway. HOXA-AS2-mediated negative regulation thus contributes to the fine-tuning of apoptosis during ATRA-induced myeloid differentiation in NB4 cells.
- Zhao H, Zhang X, Frazão JB, Condino-Neto A, Newburger PE. (2013) HOX antisense lincRNA HOXA-AS2 is an apoptosis repressor in all trans retinoic acid treated NB4 promyelocytic leukemia cells. J Cell Biochem [Epub ahead of print]. [abstract]
The field of lncRNA research is in the midst of a rapid discovery phase, but that doesn’t mean your reagents have to be“experimental”. In collaboration with Biogazelle, we’ve designed SmartChip Human lncRNA-1 Panels to maximize your investigation of lncRNA expression. They contain over 1700 triplicate, predispensed PCR assays that have been extensively validated and annotated. In addition, we’ve ensured that the lncRNA assays in this SmartChip Panel are both compliant with the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines, and curated against the latest versions of genomic databases.
To understand lncRNA expression levels across a wide variety of well-characterized biological samples and simultaneously validate the the SmartChip Human lncRNA Panel, we profiled lncRNA expression in the NCI-60 cell lines. These are a set of 59 human, cancer cell-lines derived from diverse tissues, such as brain, blood, bone marrow, breast, colon, kidney, lung, ovary, prostate, and skin. As can be seen in figure below, the resulting heatmap shows that 97% of the 1700 lncRNA assayed are expressed reproducibly in at least one of the cell lines. A snapshot of the tissue-specificity, that appears to be a hallmark of lncRNA expression, was confirmed with well-characterized HULC and GOMAFU lncRNAs.
The SmartChip Human lncRNA1 Panel is ideal for profiling the new and important area of ‘dark matter’ RNA. Simply prepare your sample, and load it into the SmartChip Panel already containing optimized real-time PCR assays in quadruplicate for each of the over 1700 assays with 10 known assays which have stable expression and can be consider ‘endogenous’ controls, and 5 exogenous RT-PCR controls; and reap high-quality results.