Iron Response ElementS

DISCUSSION

A crucial point for understanding the interactions between elements that are present in living organisms is achieving to the knowledge of their secondary and tertiary structure. Consequently, an aspect essential for understanding the function and the cellular regulation as well.

Protein synthesis can be regulated by different processes like post-transcriptional regulation, 
in which Iron Regulatory Elements (IREs) can take part. These elements are a secondary structure founded in some specific mRNAs and they can influence in their translaion. 

The objective of this project is finding a pattern for these structures called IREs. Once we found them, we observed that they really differ from different groups of sequences:

- their localization in the mRNA sequence: 3'or 5'
- their structure: four or five buldges on the first case (3') and only one on the second one (5')


In order to determine if all these structures (IREs) had a high stability and were biologically functional, we decided to use the RNAfold program to obtain the minimum free energy of the thermodynamic ensemble structures. The negative results obtained showed that they were quite stable although some of them did not correspond to the predicted structure that we have done at the beginning.

After doing that, we assessed the sensitivity and specificity for each pattern to see their reliability once run on a set of sequences.The results corroborated that our patterns were restrictive and specific due to the fact that we had not many sequences at the beginning and moreover, they were very similar ones to others.

At that point, we decided to establish cut off values because after running the patterns through the sequences we wanted to distinguish between lower (not reliable) and higher (reliable) values. With this threshold we could eliminate the sequences that probably had a low reliability.

The patterns of transferrin and ferritin were the most reliable ones because both had a quite high number of sequences. After running the patterns on the sequences we obtained encouraging results although being so restrictive.

We tracked all the data base with the ferritin and transferrin predictions. We did not use aconitase and ferroportin patterns because of the low number of original sequences that we had. 
The results showed all the initial structures and some extra sequences that we did not check but that we suppose that are mRNAs regulated by the secondary structure of IREs.