Understanding Bridge Rna Potential

Functional Role of Bridge RNAs Bridge RNAs (bRNAs) are key noncoding RNA molecules that play important roles in cellular processes as intermediaries between various RNA species. Unlike other RNAs, bRNAs do not encode proteins, but rather influence the regulation of gene expression, thereby controlling important biological functions. One of the key functions of bRNAs is their ability to form complexes with messenger RNAs (mRNAs) and other noncoding RNAs, facilitating communication within the cellular RNA network. These interactions allow bRNAs to regulate the stability, translation, and localization of mRNAs, effectively influencing the synthesis of proteins that are essential for cellular function. bRNAs are also involved in regulating alternative splicing, a process that allows a single gene to produce multiple proteins. By interacting with splicing factors, bRNAs help determine which mRNA variants are produced, thereby promoting protein diversity within the cell. In addition, bRNAs can act as molecular scaffolds that bring together different proteins and RNAs to form functional complexes that drive a variety of cellular activities. Studies have also shown that bRNAs play a role in responding to cellular stress and regulating apoptosis, a programmed cell death required to maintain tissue homeostasis. Overall, the ability of bRNAs to influence such a wide range of cellular functions highlights their importance in health and disease, making them a focus of current biomedical research. Reference [1] Matthew Durrant et al., Nature 2024 (https://lnkd.in/en7wxEdR) #BridgeRNAs #GeneRegulation #NonCodingRNA #CellBiology #RNAResearch #MolecularBiology #GeneExpression #BiomedicalResearch

What Is the “Bridge RNA” recombinase system and is it going to replace CRISPR? When Jennifer Doudna and Emmanuelle Charpentier discovered CRISPR-Cas9 in 2012, it sent shockwaves through the entire field of medicine. Scientists could finally induce sequence-dependent cuts in the DNA at (practically) any location throughout the genome allowing for precise genetic editing with ease - something that is either very difficult, or downright impossible with earlier forms of DNA editing tech. However, there are some limitations that may reduce the use of CRISPR in the clinic. Mainly, i) off-target effects (cutting at unintended sites throughout the genome) can result in permanent, unpredictable genetic alterations, ii) it can be difficult to insert large chunks of DNA, so its potential for gene delivery is limited, and iii) the Cas nuclease induces a double-strand DNA break which tends to trigger the cell’s DNA damage response and can interfere with the editing process. There are several groups working on improving CRISPR technology to overcome these limitations. However, two papers published in Nature (linked in comments) last week Friday described the discovery of a bacterial transposon-recombinase system that involves a very interesting piece of RNA that is being referred to “Bridge RNA”. Some people are saying that this may actually be a superior genome editing technology than CRISPR… Here’s how it works. Put simply, Bridge RNA are long non-coding RNAs that form two main loops (blue and orange regions in the graphic). These loops can form homology-mediated base pair interactions with two separate regions of DNA - acting like a bridge between the two pieces of DNA, drawing them close together. The Bridge RNA also binds to a recombinase enzyme (an IS110 recombinase to be precise) that, when brought into close proximity with the two pieces of DNA bridged by the RNA, will catalyze the recombination between the two. The thing is, the regions of the Bridge RNA that form sequence homology appear to be very “programmable”, meaning they can be customized to match any two pieces of DNA, which allows for sequence-specific recombination… This is huge. Sequence-specific recombination will empower highly accurate and efficient gene insertions, deletions, and inversions all without the need for the indiction of double stranded DNA breaks. It’s hard to totally capture the potential of this technology in a short LinkedIn post, just know that this is going to an EXTREMELY valuable tool - for both research and medicine - once the tech is optimized for mammalian cells. Check out the papers linked in the comments.

What's a Bridge RNA?! 🔬Let's dive into this BRAND NEW Gene Editing Mechanism: 🧬 Insertion Sequence (IS), specifically, IS110 family elements are cut-and-paste mobile genetic elements (MGEs). They 𝐞𝐱𝐜𝐢𝐬𝐞 𝐭𝐡𝐞𝐦𝐬𝐞𝐥𝐯𝐞𝐬 from the genome without leaving a scar, forming a circular intermediate during transposition. Unlike other insertion sequences, IS110 elements use a 𝐃𝐄𝐃𝐃 𝐜𝐚𝐭𝐚𝐥𝐲𝐭𝐢𝐜 𝐦𝐨𝐭𝐢𝐟 in their recombinase. This motif shares homology with RuvC Holliday junction resolvases, indicating a unique mechanism. 🧬 𝐓𝐡𝐞𝐲 𝐢𝐧𝐭𝐞𝐠𝐫𝐚𝐭𝐞 𝐃𝐍𝐀 𝐢𝐧 𝐚 𝐬𝐞𝐪𝐮𝐞𝐧𝐜𝐞-𝐬𝐩𝐞𝐜𝐢𝐟𝐢𝐜 𝐦𝐚𝐧𝐧𝐞𝐫, often targeting repetitive elements in microbial genomes. 🔍 Research shows that the circular form of IS110 drives the expression of a non-coding RNA (ncRNA) with 𝐭𝐰𝐨 𝐛𝐢𝐧𝐝𝐢𝐧𝐠 𝐥𝐨𝐨𝐩𝐬 𝐭𝐡𝐚𝐭 𝐫𝐞𝐜𝐨𝐠𝐧𝐢𝐳𝐞 𝐭𝐡𝐞 𝐈𝐒𝟏𝟏𝟎 𝐃𝐍𝐀 𝐝𝐨𝐧𝐨𝐫 𝐚𝐧𝐝 𝐢𝐭𝐬 𝐭𝐚𝐫𝐠𝐞𝐭 𝐬𝐢𝐭𝐞. This bridge RNA facilitates DNA recombination through direct base-pairing  interactions. The binding loops of bridge RNA can be reprogrammed to bind diverse DNA sequences.🤯 This modularity could support a general mechanism for DNA rearrangement, enabling sequence-specific insertion, inversion, and excision!!! Is this the end of CRISPR?! What do you think?🤔 #biotechnology #crispr #innovation #technology #genetherapy