miRNA and RISC: What's the point?

[Genecks]

Alright, I've tried reading up about miRNA and RISC, but I still lack an understanding of their functions.

 

So, let me see if I get this right.

 

1. The nucleus generates a piece of double stranded miRNA.

2. The double stranded miRNA gets captured by a RISC

3. If the miRNA matches some part of the RISC, then the miRNA is destroyed.

 

Right? Wrong?

 

I've been reading that somehow this process slows down mRNA translation?

I don't see how that works.

I've read wikipedia, but has yet to help.

[CharonY]

Nope. The microRNA is part of the RISC complex. Together they they act on mRNA.

[Genecks]

Let's see if I get the idea:

 

1. Gene encodes for mRNA

2. Some other gene codes for miRNA (but won't be transcribed yet)

3. mRNA is released to cytoplasm

4. mRNA starts forming proteins

5. After a certain amount of proteins are built, a signal is created to induce miRNA to be expressed

6. miRNA is created and released to the cytoplasm

7. It undergoes alterations, such as dicing

8. The miRNA binds to RISC to make a RISC complex

9. From there, the RISC complex binds to the mRNA that has been making proteins

10. The RISC complex shuts down that mRNA, and perhaps creates some signal that prevents the mRNA that was making proteins from being transcribed again

 

The reason the RISC complex exists is because organisms needed a way to degrade mRNA.

Otherwise, mRNA would continually build proteins and whatnot.

Right?

 

Are we to say that before the early-1990s that modern scientists did not think or consider that a process existed to degrade or control mRNA?

Edited December 7, 2009 by Genecks

[CharonY]

The RISC complex is far from being the only system controlling mRNA stability. It is but one of many layers of regulation. In addition the regulatory cascade can be very complicated and is often not governed by the gene product of the target. They can e.g. be present to maintain certain equlibria, triggered by certain stimuli, be involved in feedback inhibition of metabolites and so on.

[dttom]

The sequence is not necessary to be mRNA first then miRNA and RISC formation, it could be reversed so the activity of the later transcribed mRNA is controlled, says if the RISC recognises that mRNA and binds to and degrades it, but there is still a portion of which has yet been degraded, in addition to transcription of mRNA. So activity of mRNA is regulated. A copy of miRNA could bind not only to one species of mRNA so there is a potential of a diversity in cross-regulation.

 

To your thought that scientists before 90s have not thought about a regulatory mechanism for mRNA functioning, I'm not sure, but it should be more plausible if you considered they have not found such a mechanism.

[CharonY]

Several mechanisms pertaining to mRNA stability are known for much longer. However the regulatory role of small RNAs (again, it is not the sole regulator) is a rather novel aspect.

Thinking of the regulation as a series of defined switches is often not applicable. Generally you always have a equlibrium reaction. The level of the RISC complex (together with the status of other regulatory elements) regulate the total amount of protein being produced. Each of the circuits can and often are responsive independently from each other.

Quite often you will find that a given mRNA is produced (as long as there is no transcriptional repression) and then the due to some factor (or lack of it) the mRNA gets degraded (by RISC and other processes) with only low level of protein translation.

Bottom line: things are always a degree of magnitude more complicated than one thinks it is.