hgheith
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If anyone can help me with this Q I would really appreciate it.
I dont have an answer but this came up from a friend:
What would a deletion of the first exon do to mRNA or protien?
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| hgheith
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There was a Q in the biochem kaplan lectures similar to this at the end of chapter 4, someone please correct me if I'm wrong in deducing the answer :?
Translation of the first exon in certain protiens (ones being secreted, placed on the cell membrane, or directed to lysosomes) yeilds an N-terminal hydrophobic signal sequence which targets the ribosome to the ER (now RER) with the help of signal recognition particle. (this sequence is cleaved later in the ER)
:?: SO if the first exon was deleted this sequence would not be translated, and the ribosome would never reach the ER. the product protein would then accumulate in the cytoplasm instead of going to it's target.
The Q in the lecture notes was about parahemophilia which has this deleted sequence.
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| Malaysian
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My understanding is that the first exon starts off with the AUG SEQUENCE FOR PROTEIN synthesis if its not there most likely the RNA will not end up being translated and degraded incase.....hgheith has some valid points too
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| dariush
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the first Exon (starting with AUG) is needed for post-transcriptional Capping on the 5' which is recognized by Ribosom.
no 1st exon --> no 5' Cap --> no translation
besides 5' cap also inc. the mRNA half-life, w/o it mRNA doesnt live long !!
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| tonguo
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agree with hgheith, the protein will still be translated. the ribosome will scan through the mRNA and find the next AUG codon to start translation. mRNA could still be capped and tailed, but shorter w/o 1st exon. if the protein is originally to be secreted etc, then now it accumulates in cytoplasm. the function may also be affected.
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| dariush
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tongou, i think you misunderstood.
it is the 5' CAP which is recognized by ribosome and THEN ribosome scans through the mRNA to find the first AUG. so if there is No capping Ribosome can not cling to mRNA at all,let alone scan for the next AUG.
anymore ideas guys?
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| tonguo
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dariush, upstream of the 1st exon, there is 5' UTR. that is where the 5' cap is added. if only the 1st exon is deleted at DNA level, the UTR region in mRNA will be intact. evidence that transcripts missing 1st exon could still be translated can be found in a Q about parahemophilia in Kaplan notes as mentioned by hgheith. what do u think, dariush?
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| dariush
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tonguo, EXON and ENTRON matter at the RNA level. before transcription there is no distinction. abviously when we are talking about an EXON deletion we are speaking of a "Splicing error" which misses the cutting point b/w the 1st Exon and Entron and therefore they together dettach from the rest of the RNA. um sure u wouldnt expect a point mutation (i.e. bp deletion) at DNA level to be able to omit the WHOLE first EXON. would u?
now, we will go through the story together :
after mRNA is transcribed, it's 5' and 3' are modified (u know the details) which includes Capping at 5'. then Splicosomes begin splicing the hnRNA.
so far so good. but if for some reason at this level splicing of the first point doesnt happen, what happens?
this is the scheme :
5'Cap------UTR--------|AUG----1st exon----------|--------1st entron----------|---2nd exon--------
if the point b/w the 1st exon + 1st entron is NOT cut but the point b/w 1st ent + 2nd exon is cut as expected, we will have the mRNA as below :
|-------2nd exon--------|---------3rd exon---------|---
as you can see the CAP is gone too!!
hope that helped.
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| tonguo
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hi, darish, i appreicate ur explanation. no offense, but i am still not convinced. i dont know if there is a capping signal. if so, i would think its located in 5' UTR, just as polyadenylation signal is in 3'UTR. so i think the mRNA should look like this (mature mRNA with introns deleted):
5'CAP----UTR----&&&&&&&2nd exon&&&&&&~~~~~3rd exon~~~~~=====UTR=======AAAAAA
i hope sb. else can help us out here.
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| Malaysian
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Hi,
I too feel there is no capping signal translated on the first exon as pointed out by tonguo.All I know the first thing to be coded in mRNA is for methrionine protein.and so when u remove the first exon the AUG goes and so no protein is formed.Anyway who cares!!!Just remember that the RNA ain't going to be trnaslated and so will be degraded.
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| dariush
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hi Tongou, i enjoy talking to you.
i just can`t help wondering if the 1st Exon is deleted, how Could the 5`CAP---UTR---- part dettach from the deleted 1st Exon and REattach to the 2nd Exon.
i am really confused. do you know any enyzme that can break the
-----UTR----|---1st Exon---- connection ? so that only the 1st exon is missing? tell me what you think?
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| tonguo
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hi dariush, the same to you. i really don't know if there is an example for 1st exon deletion in nature. if this does occur, i would think it is by a SD signal-like sequence somewhere in UTR or 1st Intron that interacts with SA signal of 2nd Exon. SD/SA signals r very short and the chance that similar sequence occur somewhere other than start and end of an exon is appreciable.
but this can be easily done by recombinant DNA technology, and i think the protein can still be translated. but its shorter and may have defective function.
hope i am not adding more confusion here.
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