26
Jan
09

RNAi

Well, since Abbie doesn’t want to talk about RNAi, I suppose I will. As with my more technical posts, I’ll try to define all the not-so-common terms first.

mRNA=active RNA transcripts with introns removed

miRNA=small RNA sequences (~20 bases) which may be complementary to an mRNA transcript

dsRNA=double stranded RNA; necessary to start the RNAi pathway

Dicer=a protein which cleaves dsRNA

siRNA=small interfering RNA; small segments of dsRNA which have been cleaved by Dicer

RISC=RNA-induced silencing complex, a large protein and RNA complex which binds the antisense segment to an mRNA transcript

HIV transactivator (Tat)=one of two subtypes of proteins which increase the level of HIV expression

TAR=transactivation response region, a portion of RNA which reacts to Tat by forming a stem loop of dsDNA

Now, Tat has an RNA binding domain as does Dicer, and since Dicer is required to initiate RNAi, when Dicer binds to TAR (this is dsRNA) which is also the target of Tat, Tat then interacts with the helicase region of Dicer and suppresses the RNase activity. This suppression of Dicer at the location where it would interact (TAR) prevents the formation of RISC and the degradation of the HIV transcript.

Additional reading:
HIV-1 Tat interaction with Dicer: requirement for RNA. Bennasser et al. Retrovirology 2006 3:95
HIV-1 TAR RNA Subverts RNA Interference in Transfected Cells through Sequestration of TAR RNA-binding Protein, TRBP. Bennasser et al. J. Biol. Chem., Vol. 281, Issue 38

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7 Responses to “RNAi”


  1. January 27, 2009 at 3:12 pm

    I want to say something funny to lighten this up a bit, so, “I’ve gota head full of introns, and they’re driving me insane!”

    Now that I’ve gotten over that, I have a real comment.

    Actualy a question. What is the difference between HIV and HTLV?

  2. 2 jaredcormier
    January 27, 2009 at 7:44 pm

    Generally, HTLV (Human T-lymphotropic virus) is a virus which sometimes results in leukemia, HIV (which was formerly called HTLV-III) results in low white blood cell counts. Both are retroviruses, but they are pretty different in terms of evolution.

  3. 3 Colloquy
    January 28, 2009 at 7:52 am

    Does HTLV produce a higher white blood cell count?

  4. 4 jaredcormier
    January 28, 2009 at 7:30 pm

    Yes, it does, it activates a subtype of T-helper cells (Th1) cells which result in suppressed Th2 (another subtype) proliferation. The activation of Th1 cells results in increased levels of Interferon gamma (IFN-γ) and Tumor Necrosis Factor alpha (TNF-α), the former (IFN-γ) results is what causes the suppression of Th2 cell proliferation.

  5. 5 Colloquy
    January 28, 2009 at 7:39 pm

    Interesting. The reason I ask is … there seems to be some interest in finding a link between MS and leukemia.
    http://www.admin.cam.ac.uk/news/dp/2008102203
    … and Abbie often refers to a link between HIV and MS.
    Hmmmm… 😕

  6. 6 Colloquy
    January 28, 2009 at 7:45 pm

    R U moderating posts with links?

  7. 7 jaredcormier
    January 28, 2009 at 7:56 pm

    no, I don’t think so
    [fixed] I was

    Yea, I’d heard that, haven’t really read the literature on it yet, though.


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