#circularrna

[newsababil360]

Self‑Replicating Circular RNA Thrives in Boiling Springs: What It Means for Life’s Origins

# RNA Defies the Heat: Circular Molecules Multiply in Yellowstone’s Boiling Pools In a breakthrough that overturns decades‑old assumptions about the fragility of RNA under extreme conditions, scientists have discovered self‑replicating circular RNA thriving in the scalding waters of Yellowstone National Park’s hot springs. The finding demonstrates that these minimalist genetic loops not only survive temperatures that were thought to denature nucleic acids but actively copy themselves, forming a resilient microbial consortium that could reshape theories of life’s earliest chemistry. ## Key Takeaways - **Circular RNA persists in >70 °C waters**: The study confirms that circular RNA remains stable and functional in geothermal environments previously deemed inhospitable to nucleic acids. - **Active self‑replication observed**: Laboratory analyses show the RNA loops undergo autonomous templated replication, a hallmark of primitive genetic systems. - **Implications for abiogenesis**: The results provide concrete evidence supporting RNA‑centric origin‑of‑life models, suggesting that early Earth’s hydrothermal niches could have fostered RNA‑based chemistry. - **Resilient microbial community**: The replicating RNAs are part of a broader consortium of extremophiles, indicating cooperative networks may have been essential for early biochemical evolution. - **New experimental avenues**: The discovery opens pathways for synthetic biology to harness thermostable circular RNAs for biotechnology and therapeutic applications. [Read Full Article](https://news.ababil360.com/self-replicating-circular-rna-thrives-in-boiling-springs-what-it-means-for-lifes-origins/) #CircularRNA #Yellowstone #HotSprings #Abiogenesis #RNAWorld #ExtremeLife #MolecularBiology #OriginsOfLife #SelfReplication #newsababil360

[torontostudent]

Biogenesis and Functions of Circular RNAs (Part 1)

In a more detailed view of how circular RNAs can be generated during splicing, let’s now consider the example of an RNA with 4 exon segments and introns between each of them. If the introns after exon 1 and the intron before exon 4 contain reverse complementary sequences, they can base pair together and a loop resembling a hairpin structure. This results in exons 2 and 3 being lined up next to each other with the end of exon 3 being right next to the beginning of exon 2, which gives them an opportunity to circularize. Thus the end of exon 3 attacks the head of exon 2 and forms a circular RNA. If the intron between exons 2 and 3 are not spliced out, it results in an Exonic Intronic Circular RNA (EIciRNA). If canonical splicing occurs on this circular RNA then the intron will get spliced out and we get a circular RNA with only exons 2 and 3, which forms an Exonic Circular RNA (ecircRNA).

There is also circularization that is driven by RNA-Binding Proteins (RBP). A complex of two RNA-binding proteins that are bound to each other could come in at the previously mentioned introns and then bind onto them to create the same loop with the head of exon 2 right next to the tail of exon 3. Then the tail of exon 3 attacks the head of exon 2 and the same process of circularization occurs again.

There is also lariat-driven circularization. In this, the tail of exon 1 directly attacks the head of exon 4. This results in the introns next to exons 1 and 4 being joined in a lariat structure, with exons 2 and 3 still attached to the introns and exons 1 and 4 being cleanly joined together without the introns in between them. Then in this lariat structure, the tail of exon 3 is close to the head of exon 2 again since their introns are joined together at the top, so exon 3 attacks exon 2 again and circularization occurs.

As for the function of circular RNAs, the Exonic Circular RNAs (ecircRNA) can act as either micro RNA (miRNA) sponges or RNA-Binding Protein (RBP) sponges. Each circular RNA can allow a bunch of micro RNAs or RNA-Binding Proteins to bind to their outer surface, so they effective ‘soak up’ any free-floating micro RNAs of RNA-Binding Proteins in the area. The micro RNAs that are soaked up by the ecircRNAs are actually bound to argonaute (AGO) in a complex, so the argonaute-microRNA complexes are bound to the circular RNA if the circular RNA has binding sites that can take in microRNAs. An example of RNA-Binding Proteins that circular RNAs can soak up is the Muscleblind protein (MBL).

Exonic Intronic Circular RNAs (EIciRNA) can act as a regulator of transcription. It does this by having the intronic segment of the circular RNA interact with RNA Polymerase II in the cell while the exonic segments can attach to the promoter before the gene that is supposed to be transcribed. These exonic intronic circular RNAs are retained in the nucleus because that’s where transcription occurs, and they first interact with the U1 small nuclear ribonucleoproteins (snRNP). The place that interacts with U1 is the 5’ splice site of the intron that was retained in the circular RNA. Then that’s when RNA Polymerase II comes and joins up with them on the promoter of the gene, and this stimulates initiation of transcription. The EIciRNA is able to recognize the gene that it needs to promote because it actually promotes the genes that the circular RNA was made from, so the exonic portions of the circular RNA are suitable for binding onto those genes near the promoter.

In summary, there are three main ways that exonic circular RNAs and exonic intronic circular RNAs are generated. The first is through intron base-pairing-driven circularization, and the second is through RNA Binding Protein pairint driven circularization. These two form the same structure and result in a circular RNA. The third is lariat-driven circularization which results from exon skipping. This ultimately leads to the possibility of the same circular RNA being generated, but this is different from the other two in that due to exon skipping, in addition to the circular RNA we can also get an additional linear mRNA product.

[torontostudent]

Big Concepts of Circular RNAs

Endogenous circular RNAs mainly perform post-transcriptional gene regulation. This includes being involved in the canonical splicing of introns. There are two ways that introns are spliced, which is canonical and non-canonical splicing. Canonical splicing is the main way that splicing occurs (more than 99% of splicing is canonical) and it requires the intro to start with a GU at the 5’ end and end with an AG at the 3’ end. CircRNAs are also involved in the joining of exons to produce the functional mRNAs after they are transcribed.  

Research has shown that many products of exon scrambling (non-canonical splicing which results in joining of exons in a not normal order) are circular RNAs. The ends of some exons can end up circularized with the ends of other exons that it comes into contact with during exon scrambling.

Circular RNAs can also act as miRNA sponges, which means that they bind micro RNAs, as well as bind to some important cellular proteins which results in the ability of circRNAs to control the regulation and dysregulation of gene expression. This is because the miRNAs and proteins regulate gene expression so by binding these things, circRNAs can control how many miRNAs and these proteins are floating around in the cell. One other important thing though, is that cancer can arise from dysregulation of gene processing, so it is possible that cancers and other diseases also hijack the production of circular RNAs in order to dysregulate the cell in the disease’s favor. Thus, circRNAs are a potential biomarker for detection and future treatment of cancers and other diseases.