Expanding Universe of Noncoding RNAs

From CRISPR to Pervasive Transcription

CRISPR and Noncoding RNAs: Evolutionary Defenses

Noncoding RNAs, small interfering RNAs, and Piwi-interacting RNAs are crucial molecules that play integral parts in the defense of cells against harmful genomic elements such as viruses and transposons. They evolve in different ways and through different mechanisms, reflecting the different ways cells cope with defense strategies.

siRNAs are derived from dsRNA, a signature of viral infections. Inside the cell, dsRNA is diced into siRNAs by the Dicer enzyme. The resulting siRNAs become part of the RISC complex, which guides the cognate mRNA targets through degradation, thus inhibiting the viruses from replicating.

In contrast, piRNAs are processed from longer genomic precursors termed piRNA clusters. Unlike siRNAs, piRNAs are generated not from any foreign dsRNAs but are encoded in the host genome itself. These piRNA clusters are transcribed into long precursor RNAs that are then processed into mature piRNAs. These piRNAs are important for silencing transposons and other potentially harmful genetic elements and thus preserve genome integrity by acting similarly to siRNAs but against endogenous elements.

CRISPR-Cas9 is a revolutionary tool adapted from bacterial defense systems, which use RNA-guided mechanisms to ward off an invader. The CRISPR loci in bacterial genomes contain short DNA sequences-usually pieces of previous viral infections-interdispersed with repeat sequences. These are next transcribed into long RNA molecules that later get processed into CRISPR RNAs, or crRNAs. Each crRNA guides Cas9 protein in recognizing and cleaving DNA with sequence complementarity to crRNA. A system evolved of attacking virus DNA was adapted to edit eukaryotic genomes in a very precise fashion whereby a guide RNA sequence along with the Cas9 protein is expressed inside a cell to induce specific double-strand breaks in DNA. This ability to induce site-specific mutations or to add new genetic information has revolutionized genetic studies and biotechnology.

The Expanding Transcriptome: Beyond Protein-Coding Genes

The term transcriptome refers to the entire collection of all RNA molecules expressed from the genome of an organism, including both coding and noncoding RNAs. Recent advances in genomics have resulted in the revelation that a vast component of the mammalian transcriptome consists of noncoding RNAs, extending our previous perception of what is truly functional regions of the genome.

Extensive transcription: It has recently been found that a large fraction of DNA in mammals is transcribed into RNA, including, until recently, regions thought to be "junk" or noncoding. This pervasive transcription encompasses not only the transcription of transposable elements but also includes regions between genes, known as intergenic regions. Because so much RNA is transcribed, the question of what the function of these transcripts might be is of interest.

Background Noise or Functional Regulation?

Another idea is that much of this transcription is simply noise, a byproduct of the complex process of gene expression. Experiments in genetically engineered mice, in which large blocks of non-coding DNA were deleted, showed that such mice could still grow up and appear normal and healthy, suggesting that the removal of certain noncoding RNAs did not cause significant effects on their viability.

Otherwise, many scientists state that non-coding RNAs play crucial roles in the regulation of cellular functions. Supporting evidence for this latter view is that the distribution of non-coding RNA was tissue and developmental-stage-specific and reproducible. Such patterns, in turn, suggest that these non-coding RNAs might be responsible for many regulatory functions, like controlling gene expression, influencing chromatin structure, and modifying cellular responses to environmental changes.

Long Noncoding RNAs: Long ncRNAs are normally greater than 200 nucleotides in length and have recently emerged as key regulators of gene expression. Examples include XIST, involved in X-chromosome inactivation; HOTAIR, which influences chromatin modifications; and AIRE, responsible for regulating the expression of tissue-specific antigens. The identification of thousands of conserved lncRNAs suggests that such transcripts are playing critical roles, although many of their functions still need to be determined.

Implications and Future Directions

The studies of noncoding RNAs-from the bacterial roots of CRISPR through to the intricacy of the mammalian transcriptome-point to an enormous regulatory web that prescribes cellular activities. While much has been learned, many aspects of noncoding RNA functions remain obscure. Further study of the functions of siRNAs, piRNAs, CRISPR systems, and numerous classes of lncRNAs will probably bring more surprises in terms of shedding light on their function in cellular processes, mechanisms of disease, and therapeutic applications. A very bright future awaits the burgeoning field of RNA biology, with much promise for further refinement in our knowledge of how the genes are regulated and for additional strategies in genetic manipulation and disease treatment.

ADVERTISEMENTS

ADVERTISEMENTS

Engage with Us:

Stay tuned for more captivating insights and News. Visit our Blogs , Science paper , Study Portal and Follow Us on social media to never miss an update. Together, let's unravel the mysteries of the natural world.