Vince and Gen’s Journal Club

random papers 

RNAi Pathway

I found an interesting introduction to the RNAi pathway on wikipedia and in the introduction of a nature review article (both attached below).

What is RNAi?

RNAi refers (as far as I can tell) to two dominant pathways:
1) The processing of dsRNA into small ~20 nucleotide bits called siRNA (small-interfering RNA)
2) The processing of imperfect RNA hairpins into miRNA (micro RNA).

In both pathways, the processing of the precursor RNA is done by an RNaseIII enzyme known as dicer. The processed siRNAs or miRNAs then associate into a RISC (RNA-induced silencing complex). The RISC then binds to a target mRNA transcript through sequence complementarity provided by the incorporated siRNA or miRNA. At this point, argonaute, a core component of the RISC, acts to cut up the mRNA transcript, destroying it and preventing expression of the gene during translation.

Picture: Overview of the RNAi pathway. Taken from Wikipedia

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Posted by Vincent Chu 

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Ancient RNAi, "beaver fever," and other random thoughts

When I read a paper, I usually have no idea what's going on until I read a bunch of other papers on the same topic.  I suppose this is because it's hard for me to determine what pieces of information are interesting or important in a paper that is outside of my field (unfortunately, I don't have a field yet...so everything is outside of my field). 

Anyhow, I actually found this paper quite interesting.  Firstly, I thought it was cool to read more about Giardia and Giardiasis ("beaver fever"). Giardia's life cycle is so interesting!  It can live in beavers, cattle, dogs, rodents, and bighorn sheep in addition to humans. Ingestion of as few as 10 cysts can cause an infection.  After ingestion, the host's acidic stomach stimulates excystation, which produces 2 trophozoites.  These are little guys with tails that swim down to the duodenum & proximal jejunum, where they attach using an "adhesive disk."  Their growth is stimulated by bile, carbs, and low oxygen, and they may cause GI distress (unknown mechanism) in 1-2 weeks of infection.  One article from 2004 claimed that they may secrete anti-inflammatory signals (unknown mechanism). 

In any case, I also learned that an international collaboration beginning in the 1990s, and really kicking off in 2000, resulted in analysis of 3 ancient genomes: Trypanosoma cruzi, Trypanosoma brucei, and Leishmania major ("Tritryps").  Another review, written in 2004, presented evidence that RNAi machinery was present in several types of protozoa, but its function was unknown.  I think this is interesting because this means RNAi (and possibly other types of noncoding RNAs) are not unique to humans.  This also gives an example of how RNAi machinery is used for survival in a hostile environment.

In the introduction, the authors state that Giardia's genome codes for more than 190 VSP genes, but they were only able to amplify 8 of them by RT-PCR with degenerate primers.  They used this nuclear run-on assay, which I am not totally sure I understand (Fig 1a).  My best guess is that they take the nucleus out of a trophozoite and add some transcription machinery and labeled nucleotides in vitro.  Only open or active areas of the genome will be transcribed in vitro.  They used this mixture of RNA to probe a membrane with little blobs ("slot blotting") of DNA encoding 8 different VSPs.  This experiment tells you that particular genes are potentially transcribed in vivo. 

A blurry Fig 1b is evidence that there is one dominant total RNA transcript (or many RNA transcripts of the same size) that contains the 3' conserved region of VSPs.

In effect, the data I see so far is supportive of their hypothesis, but not exceedingly strong.  There's a lot of supplementary data, but it's got the same issues as the data in the article ("articular data?"): blurry blots that don't rule out alternative hypotheses.

Wow, this is dense.  That's all I have for now.

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Antigenic variation in Giardia lamblia is regulated by RNA interference

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Posted by Vincent Chu 

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