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Published on: July 22, 2016
RNA-Binding Proteins as Important Regulators of Long Non-Coding RNAs in Cancer
Katharina Jonas1,2, George A Calin3, Martin Pichler1,2,3
1Division of Oncology, Department of Internal Medicine, Medical University of Graz (MUG), 8036 Graz, Austria.
Abstract:
The majority of the genome is transcribed into pieces of non-(protein) coding RNA, among which long non-coding RNAs (lncRNAs) constitute a large group of particularly versatile molecules that govern basic cellular processes including transcription, splicing, RNA stability, and translation. The frequent deregulation of numerous lncRNAs in cancer is known to contribute to virtually all hallmarks of cancer. An important regulatory mechanism of lncRNAs is the post-transcriptional regulation mediated by RNA-binding proteins (RBPs). So far, however, only a small number of known cancer-associated lncRNAs have been found to be regulated by the interaction with RBPs like human antigen R (HuR), ARE/poly(U)-binding/degradation factor 1 (AUF1), insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), and tristetraprolin (TTP). These RBPs regulate, by various means, two aspects in particular, namely the stability and the localization of lncRNAs. Importantly, these RBPs themselves are commonly deregulated in cancer and might thus play a major role in the deregulation of cancer-related lncRNAs. There are, however, still many open questions, for example regarding the context specificity of these regulatory mechanisms that, in part, is based on the synergistic or competitive interaction between different RBPs. There is also a lack of knowledge on how RBPs facilitate the transport of lncRNAs between different cellular compartments.
Insights
Long non-coding RNAs (lncRNAs) are crucial in cancer. RNA-binding proteins (RBPs) regulate lncRNA stability and localization, but their interactions and transport roles in cancer remain largely unknown.
Area of Science:
- Molecular Biology
- Cancer Biology
- RNA Biology
Background:
- The majority of the human genome is transcribed into non-coding RNAs, including long non-coding RNAs (lncRNAs).
- lncRNAs play vital roles in fundamental cellular processes and are frequently deregulated in cancer, contributing to its hallmarks.
- Post-transcriptional regulation by RNA-binding proteins (RBPs) is a key mechanism controlling lncRNA function.
Purpose of the Study:
- To explore the regulatory roles of RBPs in lncRNA stability and localization.
- To investigate the involvement of RBPs in cancer-associated lncRNA deregulation.
- To identify knowledge gaps concerning RBP-lncRNA interactions, including context specificity and intercellular transport.
Main Methods:
- Literature review of studies on lncRNA and RBP interactions.
- Analysis of known cancer-associated lncRNAs and their RBP regulators.
- Identification of specific RBPs (e.g., HuR, AUF1, IGF2BP1, TTP) involved in lncRNA regulation.
Main Results:
- A limited number of cancer-associated lncRNAs are known to be regulated by RBPs.
- RBPs primarily influence lncRNA stability and localization.
- Many RBPs are themselves deregulated in cancer, suggesting a significant role in lncRNA dysregulation.
Conclusions:
- RBPs are critical regulators of lncRNA stability and localization, with implications for cancer development.
- Further research is needed to understand the context-specific and synergistic interactions between RBPs and lncRNAs.
- The mechanisms by which RBPs facilitate lncRNA transport between cellular compartments require further investigation.
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02:39lncRNA - Long Non-coding RNAs
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Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
01:20Types of RNA
RNA Performs Diverse...
01:29Translational Regulation
01:53RNA Stability