[Ontology-editors] forward and reverse transcription

Tue Dec 2 04:34:04 PST 2008

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.

> 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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>