[Ontology-editors] forward and reverse transcription

[Karen Christie]

one further comment inline

On Tue, 2 Dec 2008, Midori Harris wrote:

> Thanks for all the thoughts so far. Comments on Karen's comments inline ...
>
> On Mon, 1 Dec 2008, Karen Christie wrote:
>
>> Hmmm, a tricky question...
>> 
>> Reading through the whole thread so far, I have several comments.
>> 
>> 1. Based on the current defs of "RNA-dependent DNA replication" (which 
>> includes the phrase 'RNA-dependent DNA polymerases (e.g. reverse 
>> transcriptase)' and of "transcription, RNA-dependent" which has 'reverse 
>> transcriptase' as a synonym, these two terms do seem to be identical.
>> 
>> However, it seems to me that the reverse transcription (txn) step is only 
>> half of "RNA-dependent DNA replication" because reverse txn only makes a 
>> ssDNA copy. This ssDNA then serves as the template for production of dsDNA 
>> (going off my old biology book). So, perhaps the def of "RNA-dependent DNA 
>> replication" needs to be broader to encompass the whole process, and 
>> "transcription, RNA-dependent" could have a part_of relationship to such a 
>> redefined/new term.
>
> That's an interesting point, and one that hadn't occurred to me, since I was 
> going by just the existing GO defs. Your proposed changes sound like they 
> would work well, assuming that reverse transcription always happens in the 
> context of dsDNA synthesis (I don't know of any non-experimental exceptions). 
> Perhaps the broader process should be named RNA-dependent DNA synthesis or 
> something to that effect, rather than use 'DNA replication' -- DNA 
> replication seems a bit odd for a process that doesn't start with DNA.

Julie and I both sort of thought that reverse txn occurs both in the 
contects of DNA replication and mRNA production. Neither of us is a viral 
expert, so we could be wrong. But if our current sense is right, then we 
probably can't have the only 'reverse transcription' term be part_of 
'RNA-dependent DNA replication'. We might need to have a general term and 
child terms that can receive appropriate parentage under DNA replication 
etc. So, it seems that we need to get a better sense of the biological 
contexts of reverse transcription before proceeding.

-Karen


>> 2. Harold's example of "A negative-sense ssRNA virus genome is copied by an 
>> RNA polymerase to form positive-sense RNA" is currently outside the scope 
>> of the question at hand, since this is not included in either form of 
>> transcription represented in GO by current defs:
>> - txn, RNA-dependent =  ssDNA copy from RNA template
>> - txn, DNA-dependent = ssRNA copy from DNA template
>> 
>> I'm definitely not an expert on all the ways viruses can do things, so it 
>> may be that we need to represent making a ssRNA copy from an RNA template, 
>> but this is currently not included in the def of "txn, RNA-dependent".
>
> I think we'll need a new child of RNA biosynthetic process for this. Also 
> mRNA transcription has mRNA biosythesis, mRNA biosynthetic process and mRNA 
> synthesis as broad synonyms. Although the 'broad' scope is correct, we 
> probably ought to remove those synonyms and create a new term instead. Even 
> if we don't, the viral processes as in Harold's example are still making RNA 
> from RNA, and therefore are not transcription. (The rRNA and tRNA terms also 
> have corresponding synonyms, but I don't know of any viruses that encode rRNA 
> or tRNA ...)
>
>> 3. While I see where Harold is going in the idea that it's "all in what the 
>> copy is used for", I'm not sure that we can use this to distinguish. In 
>> terms of how enzymologists think of reverse transcriptase, it's the enzyme 
>> that makes a ssDNA copy from an RNA template.
>
> I agree with Karen here -- we can't use "what the copy is used for" to 
> determine whether a given process is transcription. It doesn't make any sense 
> for GO to abandon the definition of transcription that the molecular biology 
> community has long established; it's poor ontological practice to define a 
> process in terms of events that happen after the process itself has ended; 
> and there would be immense (and absurd) practical problems as well. For 
> example, what if an mRNA is synthesized, but then degraded before it's 
> translated into protein? Does that mean that the process by which it was 
> synthesized wasn't transcription after all?
>
>> 4. Thinking about the question "Should "txn, RNA-dependent", e.g. reverse 
>> txn be uder "gene expression", I talked to my coworker Julie, who is more 
>> knowledgable about viruses than I am, and we weren't sure that "reverse 
>> txn" could be classified as always "gene expression" or as always 
>> "RNA-dependent DNA replication"; it seems that reverse txn is used in both 
>> contexts. In addition, once you start considering viral life cycles, is it 
>> always true that "txn, DNA-dependent" is part of "gene expression" or are 
>> there viruses that use DNA intermediates in the process of making an RNA 
>> genome?
>
> In a sense, all retroviruses do this -- the dsDNA produced by reverse 
> transcription + second strand synthesis can be integrated into the host 
> genome, where host transcription machinery synthesizes RNA molecules that are 
> effectively new copies of the viral RNA genome.
>
> So I think we've convinced ourselves that the generic 'transcription' term 
> should not remain part of gene expression. I'm pretty confident that we can 
> put DNA-dependent transcription down as part of gene expression instead.
>
> m
>
>
>> 
>> -Karen
>> 
>> 
>> On Mon, 1 Dec 2008, Harold Drabkin wrote:
>> 
>>> It's all in what the copy is used for I think:
>>> 
>>> I suppose an RNA dependent RNA polymerase  vs a DNA dependent RNA 
>>> polymerase... vs ....
>>> 
>>> In the case of some single strand viral genomes:
>>> 
>>> A negative-sense ssRNA virus  genome is copied by  an RNA polymerase to 
>>> form positive-sense RNA. This means that the virus must bring along with 
>>> it the RNA-dependent RNA polymerase enzyme. The positive-sense RNA 
>>> molecule then acts as viral mRNA, which is translated into proteins by the 
>>> host ribosomes.
>>> 
>>> A positive-sense ssRNA viruse genome is directly used as an mRNA, making a 
>>> single protein which is modified by host and viral proteins to form the 
>>> various proteins needed for replication. One of these includes 
>>> RNA-dependent RNA polymerase, which copies the viral RNA to form a 
>>> double-stranded replicative form, in turn this directs the formation of 
>>> new virions.
>>> 
>>> Both processes use an RNA template and make an RNA. one is transcription, 
>>> the other replication.
>>> 
>>> hjd
>>> 
>>> Midori Harris wrote:
>>>> Wait, I'm confused now about what you guys favor. RNA-dependent synthesis 
>>>> of RNA isn't transcription at all; it's RNA replication.
>>>> 
>>>> Transcription is the interconversion of DNA and RNA by synthesizing one 
>>>> on a template made of the other. Synthesis of RNA on a DNA template is 
>>>> considered "forward" because it's by far the more common direction.
>>>> 
>>>> m
>>>> 
>>>> On Mon, 1 Dec 2008, David Hill wrote:
>>>> 
>>>>> I agree with Harold.  Reverse transcription refers to the process of 
>>>>> reversing the transcription process, not a type of transcription.
>>>>> 
>>>>> Harold Drabkin wrote:
>>>>>> Hmm, from  the def of 64101, the term name really doesn't fit, since to 
>>>>>> me, RNA -dependent transcription would be a process whereby an RNA 
>>>>>> template is transcribed to create another RNA molecule. As it's 
>>>>>> defined, it is "reverse" transcription.
>>>>>> Based on the def, I would vote to merge them.
>>>>>> Posted to SF also
>>>>>> 
>>>>>> 
>>>>>> Midori Harris wrote:
>>>>>>> Hi,
>>>>>>> 
>>>>>>> A couple of questions have come up in SF 2354289:
>>>>>>> 
>>>>>>> 1. Should these terms be merged?
>>>>>>>
>>>>>>>   id: GO:0006278
>>>>>>>   name: RNA-dependent DNA replication
>>>>>>>   def: "The process whereby new strands of DNA are synthesized, using 
>>>>>>> RNA
>>>>>>>   as a template for RNA-dependent DNA polymerases (e.g. reverse
>>>>>>>   transcriptase) that synthesize the new strands."
>>>>>>>
>>>>>>>   id: GO:0006410
>>>>>>>   name: transcription, RNA-dependent
>>>>>>>   namespace: biological_process
>>>>>>>   def: "The synthesis of DNA on a template of RNA."
>>>>>>> 
>>>>>>> 2. Should reverse transcription be considered part of gene expression 
>>>>>>> (at present it is, by transitivity, but if it shouldn't be, it's easy 
>>>>>>> to change)?
>>>>>>> 
>>>>>>> Comments here or on the SF item much appreciated.
>>>>>>> 
>>>>>>> https://sourceforge.net/tracker/index.php?func=detail&aid=2354289&group_id=36855&atid=440764 
>>>>>>> Midori
>>> 
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>> 
>