What are lncRNAs?

This group of molecules can have various sizes and their classification is divided into Small non-coding RNAs. These have a size of less than 200 nucleotidesand the Long non-coding RNAs or long non-coding RNAs which have a size of greater than 200.

There are currently more than 3000 lncRNAs discovered which are involved in different biological processes such as cell growth, proliferation, and apoptosis. These act in 4 different ways.

Mechanisms of regulation of lncRNAs.

lncRNAs are not defined by a common mode of action, and can regulate gene expression and protein synthesis in several different ways (Figure). Some lncRNAs are relatively highly expressed and appear to function as scaffolds for specialised subnuclear domains. The lncRNA possesses secondary structures that facilitate their interactions with the DNARNA and proteins. lncRNA can also bind to DNA or RNA in a sequence-specific manner. Gene regulation can occur in cis (e.g. in close proximity to the transcribed lncRNA) or in trans (at a distance from the site of transcription). In the case of chromatin modulation, the effect of lncRNA is typically gene-specific, exerted at the local level ( in cis ), however, chromatin regulation can also occur in trans.
Some lncRNAs have had their functions defined. experimentally and have been shown to be involved in fundamental gene regulatory processes including:

• Chromatin modification and structure.
• Direct transcriptional regulation
• Modulation of RNA processing events such as splicing, editing, localisation, translation and rotation / degradation
• Post-translational regulation of protein activity and localisation.
• Facilitation of ribonucleoprotein (RNP) complex formation.
• Modulation of microRNA regulation
• Gene silencing through endogenous siRNA (endo-siRNA) production.
• Regulation of genomic imprinting.

Attempts have recently been made to classify the various types of molecular mechanisms that may be involved in lncRNA function. lncRNAs can be defined as one or more of the following five archetypes:

• The archetype of signal: functions as a molecular signal or indicator of transcriptional activity.
• Archetype of decoybinds and titrates to other regulatory RNAs (e.g. microRNAs) or proteins (e.g. transcription factors).
• The archetype of the Guidetargeting: directs the localisation of ribonucleoprotein complexes to specific targets (e.g. chromatin modification enzymes are recruited to DNA).
• The archetype of scaffoldinghas a structural role as a platform on which the relevant molecular components (proteins and/or RNA) can assemble in complex or spatial proximity.

lncRNAs and different pathologies

With such a wide range of functions, it is not surprising that lncRNA plays a role in the development and pathophysiology of different diseases. Interestingly, genome-wide association studies have shown that most disease variants are found outside of protein-coding genes.
It has been found that lncRNAs are differentially expressed in several types of cancer, including leukaemia, breast cancer, carcinoma hepatocellular carcinoma, colon cancer, and cancer of the prostate. It is now known that key oncogenes and tumour suppressors including PTEN and KRASare regulated by the corresponding lncRNA pseudogenes that also act as competitive endogenous RNAs (ceRNA) or microRNA sponges. This highlights the important role of lncRNAs in oncogenesis.
Other diseases in which lncRNAs are dysregulated include cardiovascular diseases, neurological disorders and immune-mediated diseases and genetic disorders. One of the first lncRNAs to be discovered was Xist lncRNA, which plays an important role in the inactivation of the chromosome X, an extreme case of genomic imprinting. lncRNAs are present in almost all imprinted loci, arguing for an important role for lncRNAs in this form of epigenetic regulation.
lncRNAs represent a mine of gold of potential new biomarkers and drug targets. As well as a radical change in the way we understand disease mechanisms.

The challenge of studying lncRNAs

So far only a small proportion of lncRNAs have been studied. Although we can begin to classify different types of lncRNA functions, we are still far from being able to predict the function of new lncRNAs. This is mainly due to the fact that, unlike protein-coding genes whose sequence motifs are indicative of their function, lncRNA sequences are generally not conserved and do not tend to contain conserved motifs.

The main challenges of working with lncRNAs are the fact that they can be present in very low quantities (typically an order of magnitude lower than mRNA expression levels). They can overlap with the coding transcripts in both strands and are often restricted to the core.

Conclusions of their study

In short, if we could understand how all of them act, we could make great progress in the development of different therapeutic strategies for different heart diseases in humans. Either through the design of lncRNAs; to modulate the action of some of them; or through the design of lncRNAs to modulate the action of some of them. gene or new, more specific drugs to counteract the possible lack or overproduction of a non-coding RNA.

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