Answers.Body: <p>Those are the untranslated regions (UTRs). All mRNAs have a 5' UTR and a 3' UTR. These give the ribosome something to grab onto and often contain important regulatory sites such as miRNA target sites.</p>
  
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Answers.Text: I've often wondered idly about that. Are you 100% sure that *all* mRNAs will have two UTRs? Or, at least, all mammalian mRNAs, to keep things simple. The vast majority do, of course, but this is biology, the land of shades of gray and exceptions. Are there absolutely no mRNAs without UTRs?
Answers.UserDisplayName: terdon
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Answers.Text: Not all have them identified (yet) but functionally I think that UTRs are necessary. I'm no expert on translation, but even ignoring the regulatory aspect, I think they're necessary just to allow the ribosome to attach on.
Answers.UserDisplayName: Emily_Ensembl
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Answers.Text: Yes, that's what I'm wondering about too. I'm not a translation expert either, but I don't remember any such function. That, however, in no way implies that there isn't one, which is why I thought I'd ask. I'm pretty sure I've seen transcripts with no annotated UTRs, but as you say, that might just be a fault in the annotation rather than an actual biological phenomenon.
Answers.UserDisplayName: terdon
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Answers.Text: Thanks already for your answer (+ 1). So if I understand correctly, these regions should not encode for a protein as it is a untranslated region, correct!? However, in the corresponding protein fasta file, I find an amino sequence associated with the name and protein ID (see my edit). How can this be?
Answers.UserDisplayName: Cleb
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Answers.Text: Yes, the coding region encodes a protein. At either end of the coding region is a UTR.
Answers.UserDisplayName: Emily_Ensembl
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Answers.Body: <p>Although the explanation that UTR (untranscribed) regions can consist of multiple exons covers most situations, I think it is good to mention <a href="https://en.wikipedia.org/wiki/Stop_codon#Translational_readthrough" rel="nofollow noreferrer">stop codon readthrough</a>.</p>
  
  <p>This would result in a CDS (coding sequence) part of your mRNA (messenger RNA) <em>after</em> a stop codon.</p>
  
  <p>However, following the <a href="https://github.com/The-Sequence-Ontology/Specifications/blob/master/gff3.md" rel="nofollow noreferrer">gff3 format specification</a>, this should probably be encoded differently, using SO (<a href="https://github.com/The-Sequence-Ontology/SO-Ontologies/blob/master/so-simple.obo" rel="nofollow noreferrer">sequence ontology</a>) terms like SO:0000697 (gene with stop codon read through) and  SO:0000883 (stop codon readthrough).</p>
  
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Answers.Body: <p>Yes, of course. Exons are not limited to the protein coding regions. Many UTRs are in exons. In fact, you even have various cases of UTRs being multiple exons, and being spliced. </p>
  
  <p>What is strange in your file is not so much that you have exons beyond the stop codon, but that you also have them marked as CDS (coding sequence). That isn't possible, no. While there can indeed be exons in the UTRs, those are not coding and shouldn't be called CDS. That's probably just a minor nomenclature issue though and what you are looking at is a spliced UTR. </p>
  
  <p>So, the exons (or the parts of the exons) that fall between the start and stop codons will be translated, while those that fall outside that regions will not be (UTRs). </p>
  
  <p>For example, this is the exonic structure shown for <a href="http://www.ensembl.org/Homo_sapiens/Transcript/Summary?db=core;g=ENSG00000141510;r=17:7661779-7687550;t=ENST00000617185" rel="nofollow noreferrer">ENST00000617185</a>, one of the transcripts of the human P53 gene:</p>
  
  <p><a href="https://i.sstatic.net/43fYt.png" rel="nofollow noreferrer"><img src="https://i.sstatic.net/43fYt.png" alt="TP53 exonic structure"></a></p>
  
  <p>The boxes are exons and the lines are introns. The colored boxes are protein coding exons, while the empty ones are UTR exons. Note how they are also spliced and that this particular transcript has 3 non-coding exons on the 5' end and one on the 3' end. </p>
  
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Answers.Text: @Cleb no, UTRs are not translated. But I can't really help if you don't give us the gene you are looking at. Please edit your question and tell us where the data is coming from so we can also compare your gff to the predicted protein.
Answers.UserDisplayName: terdon
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Answers.Text: Thanks already for your answer (+ 1). So if I understand correctly, these regions should not encode for a protein, correct!? Funny thing is, however, if I look at the corresponding protein fasta, there is an amino acid sequence associated with it (see my edit). But, as it is not a coding sequence, this should not b the case then?
Answers.UserDisplayName: Cleb
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Answers.Text: Unfortunately, it is not publicly available, when I google for the gene name I don't get any hits. But for now it is already good to know that there is something fishy(?) going on so that I can contact the authors; just wanted to make sure that I don't miss something obvious.
Answers.UserDisplayName: Cleb
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Answers.Text: @Cleb there is nothing fishy going on at all. All (or, at least, the vast majority) of protein coding transcripts have untranslated regions (UTRs) and this is what you are showing. That doesn't mean that all of the transcript is not translated, only that the UTR regions are not translated. And what do you mean it isn't publicly available? Is this a gene prediction? All genes are publicly available.
Answers.UserDisplayName: terdon
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Answers.Text: Yes, thanks for clarifying, I am not very familiar with this topic, so I probably ask a couple of silly things :) Well, I got the file from a website where one can only download files if one is registered and as far as I understood one is not allowed to distribute the information without permission.
Answers.UserDisplayName: Cleb
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Answers.Text: I'm wondering if the CDS outside of the start-stop range is to do with different isoforms? The exons have a transcript id, and the CDS entryies have a protein_id, but the start and stop lines only have gene ids. Could be that the CDS entries and the start/stop_codon entires are from different transcript isoforms of the same gene.
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Answers.LastEditDate: 2018-09-06T09:54:24.150Z
Answers.UserDisplayName: terdon
Body: <p>I have a gff file like this (I edited the name):</p>
  
  <pre><code>scaffold_x  source  exon    2987526 2987805 .   -   .   name "foobar";transcriptId 68892
  scaffold_x  source  CDS     2987526 2987805 .   -   1   name "foobar";proteinId 68892;exonNumber 5
  scaffold_x  source  exon    2988610 2988745 .   -   .   name "foobar";transcriptId 68892
  scaffold_x  source  CDS     2988610 2988745 .   -   2   name "foobar";proteinId 68892;exonNumber 4
  scaffold_x  source  exon    2989157 2989645 .   -   .   name "foobar";transcriptId 68892
  scaffold_x  source  CDS     2989157 2989645 .   -   2   name "foobar";proteinId 68892;exonNumber 3
  scaffold_x  source  exon    2990903 2991541 .   -   .   name "foobar";transcriptId 68892
  scaffold_x  source  CDS     2990903 2991541 .   -   2   name "foobar";proteinId 68892;exonNumber 2
  scaffold_x  source  stop_codon  2990903 2990905 .   -   0   name "foobar"
  scaffold_x  source  exon    2991587 2992430 .   -   .   name "foobar";transcriptId 68892
  scaffold_x  source  CDS     2991587 2992430 .   -   0   name "foobar";proteinId 68892;exonNumber 1
  scaffold_x  source  start_codon 2992428 2992430 .   -   0   name "foobar"
  </code></pre>
  
  <p>So the <code>start_codon</code> is <code>2992428    2992430</code> and the <code>stop_codon</code> is <code>2990903   2990905</code>; I would therefore expect all the exons within this range, however, e.g. exon 5 is found in <code>2987526   2987805</code> which is clearly outside this range.</p>
  
  <p>Is there something wrong with the gff file itself or is there a plausible explanation for that?</p>
  
  <p>EDIT:</p>
  
  <p>In the corresponding protein fasta I do find an amino acid sequence associated with this prtein ID and name:</p>
  
  <pre><code>&gt;68892|foobar
  MHTGD...
  </code></pre>
  
Comments.ContentLicense: CC BY-SA 3.0
Comments.CreationDate: 2017-10-20T08:59:22.660Z
Comments.Text: Thanks for editing, but that doesn't tell us anything. We need to know the accession of the protein and/or gene you are looking at. What is `68892`? Is that the gene ID? Also, why would there not be a protein sequence associated with it? It is only the UTRs that are not translated, the rest of the exons will be.
Comments.UserDisplayName: terdon
Comments.ContentLicense: CC BY-SA 3.0
Comments.CreationDate: 2017-10-20T09:03:17.607Z
Comments.Text: @terdon See my comment below your answer. And thanks for the hint; there are indeed exons in the "correct" region which can then be translated to a protein. Feel free to expand your answer and then I am happy to accept it.
Comments.UserDisplayName: Cleb
Comments.ContentLicense: CC BY-SA 3.0
Comments.CreationDate: 2017-10-20T09:04:36.863Z
Comments.Text: I don't get what is confusing you, to be honest. I'd be happy to expand, but I don't know in what direction. It might be simpler if you come into [chat](https://chat.stackexchange.com/rooms/58858/bioinformatics) for a second and ping me (`@terdon`) there so we can figure out what is confusing you.
Comments.UserDisplayName: terdon
Tags: <gene><gff3><molecular-genetics><exon>
Title: Can exons be located outside of the coding sequence?
ThreadText: # Can exons be located outside of the coding sequence?
  
  (Asked by: username_0 on 2017-10-20)
  
  I have a gff file like this (I edited the name):
  
  ```
  scaffold_x  source  exon    2987526 2987805 .   -   .   name "foobar";transcriptId 68892
  scaffold_x  source  CDS     2987526 2987805 .   -   1   name "foobar";proteinId 68892;exonNumber 5
  scaffold_x  source  exon    2988610 2988745 .   -   .   name "foobar";transcriptId 68892
  scaffold_x  source  CDS     2988610 2988745 .   -   2   name "foobar";proteinId 68892;exonNumber 4
  scaffold_x  source  exon    2989157 2989645 .   -   .   name "foobar";transcriptId 68892
  scaffold_x  source  CDS     2989157 2989645 .   -   2   name "foobar";proteinId 68892;exonNumber 3
  scaffold_x  source  exon    2990903 2991541 .   -   .   name "foobar";transcriptId 68892
  scaffold_x  source  CDS     2990903 2991541 .   -   2   name "foobar";proteinId 68892;exonNumber 2
  scaffold_x  source  stop_codon  2990903 2990905 .   -   0   name "foobar"
  scaffold_x  source  exon    2991587 2992430 .   -   .   name "foobar";transcriptId 68892
  scaffold_x  source  CDS     2991587 2992430 .   -   0   name "foobar";proteinId 68892;exonNumber 1
  scaffold_x  source  start_codon 2992428 2992430 .   -   0   name "foobar"
  
  ```
  
  So the `start_codon` is `2992428 2992430` and the `stop_codon` is `2990903 2990905`; I would therefore expect all the exons within this range, however, e.g. exon 5 is found in `2987526 2987805` which is clearly outside this range.
  
  Is there something wrong with the gff file itself or is there a plausible explanation for that?
  
  EDIT:
  
  In the corresponding protein fasta I do find an amino acid sequence associated with this prtein ID and name:
  
  ```
  >68892|foobar
  MHTGD...
  
  ```
  
  **Tags:** gene, gff3, molecular-genetics, exon
  
  > **Comments:**
  > **username_1**: Thanks for editing, but that doesn't tell us anything. We need to know the accession of the protein and/or gene you are looking at. What is `68892`? Is that the gene ID? Also, why would there not be a protein sequence associated with it? It is only the UTRs that are not translated, the rest of the exons will be.  
  > **username_0**: @username_1 See my comment below your answer. And thanks for the hint; there are indeed exons in the "correct" region which can then be translated to a protein. Feel free to expand your answer and then I am happy to accept it.  
  > **username_1**: I don't get what is confusing you, to be honest. I'd be happy to expand, but I don't know in what direction. It might be simpler if you come into [chat](https://chat.stackexchange.com/rooms/58858/bioinformatics) for a second and ping me (`@username_1`) there so we can figure out what is confusing you.  
  
  ---
  
  ## 3 answers
  
  ### Answer by username_1 on 2017-10-20. Score: 11 | Accepted answer
  
  Yes, of course. Exons are not limited to the protein coding regions. Many UTRs are in exons. In fact, you even have various cases of UTRs being multiple exons, and being spliced.
  
  What is strange in your file is not so much that you have exons beyond the stop codon, but that you also have them marked as CDS (coding sequence). That isn't possible, no. While there can indeed be exons in the UTRs, those are not coding and shouldn't be called CDS. That's probably just a minor nomenclature issue though and what you are looking at is a spliced UTR.
  
  So, the exons (or the parts of the exons) that fall between the start and stop codons will be translated, while those that fall outside that regions will not be (UTRs).
  
  For example, this is the exonic structure shown for [ENST00000617185](http://www.ensembl.org/Homo_sapiens/Transcript/Summary?db=core;g=ENSG00000141510;r=17:7661779-7687550;t=ENST00000617185), one of the transcripts of the human P53 gene:
  
  [![TP53 exonic structure](https://i.sstatic.net/43fYt.png)](https://i.sstatic.net/43fYt.png)
  
  The boxes are exons and the lines are introns. The colored boxes are protein coding exons, while the empty ones are UTR exons. Note how they are also spliced and that this particular transcript has 3 non-coding exons on the 5' end and one on the 3' end.
  
  > **Comments:**
  > **username_1**: @username_0 no, UTRs are not translated. But I can't really help if you don't give us the gene you are looking at. Please edit your question and tell us where the data is coming from so we can also compare your gff to the predicted protein.  
  > **username_0**: Thanks already for your answer (+ 1). So if I understand correctly, these regions should not encode for a protein, correct!? Funny thing is, however, if I look at the corresponding protein fasta, there is an amino acid sequence associated with it (see my edit). But, as it is not a coding sequence, this should not b the case then?  
  > **username_0**: Unfortunately, it is not publicly available, when I google for the gene name I don't get any hits. But for now it is already good to know that there is something fishy(?) going on so that I can contact the authors; just wanted to make sure that I don't miss something obvious.  
  > **username_1**: @username_0 there is nothing fishy going on at all. All (or, at least, the vast majority) of protein coding transcripts have untranslated regions (UTRs) and this is what you are showing. That doesn't mean that all of the transcript is not translated, only that the UTR regions are not translated. And what do you mean it isn't publicly available? Is this a gene prediction? All genes are publicly available.  
  > **username_0**: Yes, thanks for clarifying, I am not very familiar with this topic, so I probably ask a couple of silly things :) Well, I got the file from a website where one can only download files if one is registered and as far as I understood one is not allowed to distribute the information without permission.  
  > **username_4**: I'm wondering if the CDS outside of the start-stop range is to do with different isoforms? The exons have a transcript id, and the CDS entryies have a protein_id, but the start and stop lines only have gene ids. Could be that the CDS entries and the start/stop_codon entires are from different transcript isoforms of the same gene.  
  
  ---
  
  ### Answer by username_2 on 2017-10-20. Score: 8
  
  Those are the untranslated regions (UTRs). All mRNAs have a 5' UTR and a 3' UTR. These give the ribosome something to grab onto and often contain important regulatory sites such as miRNA target sites.
  
  > **Comments:**
  > **username_1**: I've often wondered idly about that. Are you 100% sure that *all* mRNAs will have two UTRs? Or, at least, all mammalian mRNAs, to keep things simple. The vast majority do, of course, but this is biology, the land of shades of gray and exceptions. Are there absolutely no mRNAs without UTRs?  
  > **username_2**: Not all have them identified (yet) but functionally I think that UTRs are necessary. I'm no expert on translation, but even ignoring the regulatory aspect, I think they're necessary just to allow the ribosome to attach on.  
  > **username_1**: Yes, that's what I'm wondering about too. I'm not a translation expert either, but I don't remember any such function. That, however, in no way implies that there isn't one, which is why I thought I'd ask. I'm pretty sure I've seen transcripts with no annotated UTRs, but as you say, that might just be a fault in the annotation rather than an actual biological phenomenon.  
  > **username_0**: Thanks already for your answer (+ 1). So if I understand correctly, these regions should not encode for a protein as it is a untranslated region, correct!? However, in the corresponding protein fasta file, I find an amino sequence associated with the name and protein ID (see my edit). How can this be?  
  > **username_2**: Yes, the coding region encodes a protein. At either end of the coding region is a UTR.  
  
  ---
  
  ### Answer by username_3 on 2017-10-26. Score: 2
  
  Although the explanation that UTR (untranscribed) regions can consist of multiple exons covers most situations, I think it is good to mention [stop codon readthrough](https://en.wikipedia.org/wiki/Stop_codon#Translational_readthrough).
  
  This would result in a CDS (coding sequence) part of your mRNA (messenger RNA) *after* a stop codon.
  
  However, following the [gff3 format specification](https://github.com/The-Sequence-Ontology/Specifications/blob/master/gff3.md), this should probably be encoded differently, using SO ([sequence ontology](https://github.com/The-Sequence-Ontology/SO-Ontologies/blob/master/so-simple.obo)) terms like SO:0000697 (gene with stop codon read through) and SO:0000883 (stop codon readthrough).
  
  
  ---
  
  