Argonaute proteins in mammals, revealing individual functions

Kerkhof, LD (2012) Argonaute proteins in mammals, revealing individual functions. Bachelor's Thesis, Biology.

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Abstract

Argonaute (Ago) proteins are part of the RNA-induces silencing (RISC) complex and play a key role in RNA interference. They can bind small RNA, which leads the Ago proteins to their (partial) complementary mRNA. Ago proteins silence the gene function of the target mRNA by either RNA degradation (also known as ‘slicing’) or translation inhibition. Argonaute proteins are found not only in mammals, but also in plants, worms, fughi, archaea and certain bacteria and are highly conserved between species. In humans, there are four Argonaute proteins, Ago1-4. They are ubiquitously expressed in various cell types and seem to have overlapping functions. Only Ago-2 stands out for its unique slicer activity and is also located on a different chromosome than Ago1,3,4. The different chromosome location might be the reason only Ago2 contains the slicer activity. But why are there four different types of Argonaute proteins, when they seem to have similar functions? In Drosophila and C. elegans, the individual Ago proteins have specialized functions. Since the high conservation between species of the Ago proteins, human Argonautes might also have individual functions. However, the functions of the four humans Argonautes and the reason why there are four Ago proteins, remain unclear. Since Ago proteins are associated with several diseases like cancer, fragile X syndrome and autoimmune diseases, it is important to understand the functions of the individual Ago proteins. The aim of this paper is to learn why there are four different human Argonaute proteins and reveal their individual functions. The results show that Ago2 is not capable of operating on its own and all human Ago proteins can load the same pool of miRNAs. This rises the theory that the four Ago proteins serve as a backup mechanism in case one of the Ago proteins is deficient. The combination of different Ago proteins could be evolutionary beneficial and leads to higher survival in case an Argonaute protein is not functioning. However, the results also show that Ago3,4 expression levels are much lower in various tissues than Ago1,2 expression levels. This creates the theory that four Ago proteins are not evolutionary beneficial and Ago3,4 might disappear in the future, due to redundancy. In conclusion, it is too soon to draw solid conclusions about why there are four human Ago proteins. Both the backup theory and the redundancy theory could occur. More research is necessary to determine their individual functions and reveal why all four are required.

Item Type:	Thesis (Bachelor's Thesis)
Degree programme:	Biology
Thesis type:	Bachelor's Thesis
Language:	English
Date Deposited:	15 Feb 2018 07:48
Last Modified:	15 Feb 2018 07:49
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/10258

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