by Nikolaos Mellios, Mriganka Sur RNA acts as the intermediary between genes and proteins, but the function of pieces of More »
The abundance of long non-coding RNAs (lncRNAs) and their wide range of functional roles in human cells are fast becoming More »
The human brain is one of the most complex biological systems, and the cognitive abilities have greatly expanded compared to invertebrates without much expansion in the number of protein coding genes. This suggests that gene regulation plays a very important role in the development and function of nervous system, by acting at multiple levels such as transcription and translation. In this article the authors discuss the regulatory roles of three classes of non-protein coding RNAs (ncRNAs)-microRNAs (miRNAs), piwi-interacting RNA (piRNAs) and long-non-coding RNA (lncRNA), in the process of neurogenesis and nervous function including control of synaptic plasticity and potential roles in neurodegenerative diseases.
miRNAs are involved in diverse processes including neurogenesis where they channelize the cellular physiology toward neuronal differentiation. miRNAs can also indirectly influence neurogenesis by regulating the proliferation and self renewal of neural stem cells and are dysregulated in several neurodegenerative diseases. miRNAs are also known to regulate synaptic plasticity and are usually found to be co-expressed with their targets. The dynamics of gene regulation is thus dependent on the local architecture of the gene regulatory network (GRN) around the miRNA and its targets. piRNAs had been classically known to regulate transposons in the germ cells. However, piRNAs have been, recently, found to be expressed in the brain and possibly function by imparting epigenetic changes by DNA methylation. piRNAs are known to be maternally inherited and we assume that they may play a role in early development. The authors also explore the possible function of piRNAs in regulating the expansion of transposons in the brain. Brain is known to express several lncRNA but functional roles in brain development are attributed to a few lncRNA while functions of most of the them remain unknown. They review the roles of some known lncRNA and explore the other possible functions of lncRNAs including their interaction with miRNAs.
- Iyengar BR, Choudhary A, Sarangdhar MA, Venkatesh KV, Gadgil CJ, Pillai B. (2014) Non-coding RNA interact to regulate neuronal development and function. Front Cell Neurosci 8:47. [article]
The mechanism by which the 8q24 MYC enhancer region, including cancer-associated variant rs6983267, increases cancer risk is unknown due to the lack of protein-coding genes at 8q24.21. Here a team led by researchers at the YanBian University, China report the identification of long noncoding RNAs named cancer-associated region long noncoding RNAs (CARLos) in the 8q24 region. The expression of one of the long noncoding RNAs, CARLo-5, is significantly correlated with the rs6983267 allele associated with increased cancer susceptibility. They also found the MYC enhancer region physically interacts with the active regulatory region of the CARLo-5 promoter, suggesting long-range interaction of MYC enhancer with the CARLo-5 promoter regulates CARLo-5 expression. Finally, the researchers demonstrate that CARLo-5 has a function in cell-cycle regulation and tumor development. Overall, these data provide a key of the mystery of the 8q24 gene desert.
- Kim T, Cui R, Jeon YJ, Lee JH, Lee JH, Sim H, Park JK, Fadda P, Tili E, Nakanishi H, Huh MI, Kim SH, Cho JH, Sung BH, Peng Y, Lee TJ, Luo Z, Sun HL, Wei H, Alder H, Oh JS, Shim KS, Ko SB, Croce CM. (2014) Long-range interaction and correlation between MYC enhancer and oncogenic long noncoding RNA CARLo-5. Proc Natl Acad Sci U S A [Epub ahead of print]. [abstract]
UT Arlington biochemists say their newly published study brings researchers a step closer to understanding how the commonly used synthetic compound bisphenol-A, or BPA, may promote breast cancer growth.
Subhrangsu Mandal, associate professor of chemistry/biochemistry, and Arunoday Bhan, a PhD student in Mandal’s lab, looked at a molecule called RNA HOTAIR. HOTAIR is an abbreviation for long, non-coding RNA, a part of DNA in humans and other vertebrates. HOTAIR does not produce a protein on its own but, when it is being expressed or functioning, it can suppress genes that would normally slow tumor growth or cause cancer cell death.
High levels of HOTAIR expression have been linked to breast tumors, pancreatic and colorectal cancers, sarcoma and others.
Long non-coding RNAs (lncRNAs) are a class of newly identified non-coding RNA molecules that are emerging as key regulators of tumor initiation and development. Colorectal cancer (CRC) remains a major health problem worldwide, and there remains a need to further refine the current screening approaches as well as provide tailored diagnostic and therapeutic approaches. Multiple dysregulated lncRNAs participate in tumorigenesis through a variety of molecular mechanisms, and various regulatory factors frequently contribute to the aberrant expression of lncRNAs in CRC, thereby allowing malignant transformation. Additionally, the association of dysregulated lncRNAs with specific developmental stages and clinical outcomes indicates their potential as strong diagnostic and prognostic predictors as well as therapeutic targets. Here the authors provide a brief overview of the known functions of CRC-associated lncRNAs, describe some potential molecular mechanisms that underlie changes in lncRNA expression in CRC, and attempt to uncover their clinical and therapeutic potential.
- Xu MD, Qi P, Du X. (2014) Long non-coding RNAs in colorectal cancer: implications for pathogenesis and clinical application. Mod Pathol [Epub ahead of print]. [abstract]
Sheena Saayman, The Scripps Research Institute, will speak about HIV-encoded antisense lncRNA at the Non-Coding RNAs and RNAi Research & Therapeutics Conference, to be held June 19-20, 2014 in San Diego, CA.
Long non-coding RNAs (lncRNAs) have a wide range of roles in human cells, including their function as epigenetic modulators, which plays a pivotal role in the regulation of gene expression. Dr. Saayman, a postdoctoral fellow in the Kevin Morris lab, and her colleagues sought to characterize a human immunodeficiency virus (HIV) encoded antisense RNA transcript that was recently reported and determine its potential role in viral transcription regulation.
The intrinsic properties of this HIV-expressed lncRNA have been characterized and the lab’s data suggests that it functions as an epigenetic brake to modulate viral transcription. Suppression of this long antisense transcript with small single-stranded antisense RNAs resulted in the activation of viral gene expression. This lncRNA was found to localize to the 5’LTR and usurp components of endogenous cellular pathways that are involved in lncRNA directed epigenetic gene silencing. Collectively, this viral expressed antisense lncRNA is involved in modulating HIV gene expression and that this regulatory effect is due to an alteration in the epigenetic landscape at the viral promoter.
Dr. Saayman and other researchers in the RNA field will gather at the Non-Coding RNAs and RNAi Research & Therapeutics meeting to discuss the latest advances in targeted delivery, aptamers, and other hot topics. Attendees will enjoy