n00b guide to microRNAs

Cells can be seen as chemical machines composed of various interacting parts. These parts work in a very precise manner and are highly regulated. As such, cells are quite similar to the modern day computer that processes a lot of information. While you’re reading this article, many other process are happening in the background. You could be playing music or “legally” downloading a movie while your internet browser is open.

Ahoy there matey come on aboard me ship!

However, you don’t have all programs running simultaneously or else you’ll end up frying your computer. In the same way, the cell does not run all of the programs it has simultaneously. Genes are only opened (or “expressed” in biology nerd speak) when they are needed by the cell. Recent studies have shown that genes are regulated by a special class of RNA called microRNAs or miRNAs. But before we tackle what miRNAs are let’s first have a review of the central dogma.

Modifying the Central Dogma

You’ve probably first heard of RNA in a basic biology class. It’s usually taught in tandem with the concept of the central dogma in molecular biology. In case you forgot what it is or you were asleep when it was taught, the easiest way to remember it is: DNA->RNA->Protein. A gene composed of DNA is transcribed into messenger RNA (mRNA) and mRNA is translated to protein. That is its most basic form still taught in elementary or high school classes. [pro tip: don’t confuse miRNAs w/ mRNAs they’re two entirely different things]

https://i1.wp.com/biowiki.ucdavis.edu/@api/deki/files/225/03genessimplecomplex.gifTHIS ISN’T EVEN MY FINAL FORM

But we’ve moved on from that simple model. We now know that RNA is not just a transient intermediate of DNA. RNA is a dynamic player involved in the regulation of gene expression. One of the relatively new forms of RNA discovered is miRNA. It is a short sequence composed of 21-23 base pairs (A,C,U,G combinations) that can bind to numerous mRNA transcripts. When it binds to a particular mRNA, it signals the cell to degrade that mRNA or prevent translation into protein.

Mechanism of miRNA action

In English pls?

An easier way to understand how miRNAs work is to go back to our computer analogy. We can think of mRNA transcripts as running programs and miRNAs as task managers. Following our analogy, miRNAs can control whether individual transcripts are shut off. This control is exercised through the amount of miRNAs present in one cell. The more miRNAs there are, the more mRNAs are degraded. Hence, the effect of miRNAs on mRNA is similar to a task manager closing programs in a computer. But instead of clicking to end a program, more miRNAs are produced to silence mRNA expression.

Another difference is that there is no universal miRNA that can shut off all mRNAs. There are many miRNAs out there that exercise control over mRNAs. That’s like saying a task manager can control only a specific set of programs. But this lack of miRNA universality is actually useful for medical diagnostics. Scientists can track the expression miRNAs that regulate a set of important genes implicated in a given disease.

miRNAs in diagnostics

For instance, a miRNA that controls a set of genes related to tumor suppression can be tracked to diagnose if a patient has cancer. The expression profile of a dozen miRNAs is sufficient to say if one has this disease even before the deleterious effects manifest. This is particularly important in breast cancers or pancreatic cancers that are typically diagnosed only in their late stages. Early detection can lead to better treatment options for a patient and increase the likelihood of survival.

Harvesting miRNAs for diagnostics can potentially be done using nothing more than urine samples. In my next entry, I’ll talk about how this is made possible by newly discovered extracellular structures called exosomes or you can check this link to have a bird’s eye view of how they can be used in diagnostics.

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n00b guide to Molecular Biology

A primer on the blog series

When I tell relatives what major I’m taking up, I often get puzzled stares and the same confused questions. They immediately assume that I’m a masochistic pre-med major or that I work with some crazy stem cell shit. Of course, I laugh with them and play along with their silly jokes but I often get the urge to tell them all about the interesting things we study.

However, the difficult part in getting people to understand what we do is the large information gap that exists. I can’t explain how the dynamics of gene regulation work when they don’t even know what a gene actually is. But even if the concepts we study might seem completely foreign, I still want people to appreciate how amazing our cellular machinery is. I want people to know more about why disease progress the way they do or why cancer is such a difficult disease to treat. I want people to understand why I’m excited about my major even when the workload is insane at best.

It’s an arduous task but I do not believe it is impossible. So in my next few blog entries, I’ll *attempt* to give the uninitiated a taste of some molecular biology concepts that might appeal to the general public. For my first entry, I’ll introduce microRNAs and explain how they are important in the study of gene expression regulation and cancer diagnosis.