Monday, October 14, 2013

How it works: miRNA!

So previously, I was talking about the DNA to protein pathway.  But in real life, things aren't nearly as simple as this; there are many different mechanisms for feedback, for controlling how, when, and how many proteins are made from DNA synthesis.  Keep in mind that the raw genetic code in all of your cells, from skin to muscle to bone to organs to brain, is the same!  And yet somehow, these cells are able to differentiate, taking on many different shapes and roles.  How do they do it?

One way is through micro RNA, or miRNA!

Previously, I talked about messenger RNA, or mRNA, which is the intermediate stage between DNA and proteins.  DNA is transcribed into mRNA, which is then translated into protein.  A fairly simple two-step pathway.

But there are other types of RNA!  At least three other types that are well known, at least.  The first type is known as rRNA, and forms a specialized structure called a ribosome, which turns mRNA into protein.  The second type is known as tRNA, and is the structure that carries individual amino acids to the protein as it is being built by the ribosome.  And the third type is called miRNA, and suppresses the formation of proteins, preventing them from being translated at all!

So how's it work?  It's simple!

miRNA starts off just like any other RNA - it's transcribed from DNA.  But remember how RNA is single-stranded, while DNA is double-stranded?  And the bases in DNA match up with each other, leading to complementary binding that holds the two strands together?

Well, miRNA starts off as a single strand of RNA, about 70-90 bases in length.  The bases at either end of the strand match up with each other, however, which causes the strand to fold in half and form a loop, similar to a hairpin!  (In fact, these loops are known as hairpins in scientific terminology.)  This hairpin structure can also be known as a stem-loop.

Once a stem-loop has formed, an enzyme called Dicer approaches, and slices off the "loop" part of the stem-loop.  After this piece has been sliced off, the miRNA appears as a short little sequence, about 20-22 bases, and is double-stranded.

The next step after this is the formation of the RISC (pronounced like "risk") complex, a group of proteins that latch on to the double-stranded little miRNA.  At this point, one of the two strands is discarded, so the RISC complex contains a single piece of RNA, about 20 nucleotides long, sticking out from the big mass of proteins like a comb.

Now, that little miRNA contains a specific set of bases, and 20 bases means that this miRNA will only bind to sequences that are complementary matches - balanced opposites.  And it just so happens that certain, specific mRNAs have that exact complementary sequence!  The RISC complex uses its miRNA as a key to find matching mRNAs, and then binds to them and prevents them from being translated.  Instead, they are degraded, and that protein is not produced by the cell!

And thus, miRNA is able to lower the amount of, or down-regulate, the amount of a very specific protein in a cell, by preventing it from being made in the first place by destroying the mRNA.  Seems easy enough, doesn't it?

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