MadSci Network: Molecular Biology
Query:

Re: During transcription can mRNA transcribe several genes at the same time?

Date: Thu Mar 29 13:49:38 2001
Posted By: Chris Neale, Undergraduate, Biology, University of Waterloo
Area of science: Molecular Biology
ID: 985839135.Mb
Message:

During transcription can mRNA transcribe several genes at the same time?

The answer depends on the interpretation of the question.  To ensure that 
you get the desired information, and (perhaps more importantly) to help 
clarify the situation, I will begin with a general description and 
definition of terms before listing some precise questions and their 
answers.

The central dogma of molecular genetics is very important and worth 
memorizing.  It states that the order of information flow is from DNA to 
RNA to protein.  But it is a little more subtle than that because the DNA 
does not make the RNA and the RNA does not make the protein.  It is more 
mechanistic to say: DNA is transcribed to make RNA that is translated to 
make protein.  But how to remember the order of these phonetically 
simmilar processes?

DNA is very important and we don't want it galavanting around the cell.  
Instead, we make a copy: a *transcript*.  This transcript (mRNA) is 
smaller than, and slightly modified from, the original (DNA) but still 
contains the same information in basically the same way.  To remember the 
structural similarity of the mRNA and DNA, notice that they are both 
nucleic acids (the NA ind D*NA* and in R*NA*.)

Protein is very different from DNA and RNA.  Protein is not a nucleic acid 
and uses a completely different language to represent the same 
information.  We must *translate* the language of the nucleic acids into 
the language of the protein.

Now we make a final addition to our representation of the central dogma: 
DNA directs the process of transcription that is effected by RNA polymerase
(II) to create mRNA that directs the process of translation that is 
effeted by ribosomes to create protein.

In the preceeding paragraph, the term *directed* indicates that the 
sequence of the one directs the sequence of the other, and the term 
*effected* indicates the machinery that completes this task.  Also note 
that there are three forms of RNA polymerase.  It is RNApol(II) that 
creates mRNA (in the precursor form ... but don't worry too much about 
that, it's more of a disclaimer.)

***

Now for some questions:

Can mRNA translate anything?
No.  mRNA is a transcript that can only *direct* translation.

Can a ribosome translate anything?
Yes.  A ribosome is the machinery that can translate mRNA (but not DNA.)

Can multiple genes be transcribed at once?
Yes.  There are many copies of RNA polymerase.  Each copy can effect 
transcription, so many independant transcription events can (and do) occur 
simultaneously.

Can multiple genes be transcribed together to create a single mRNA?
Depends.  This is usually associated with prokaryotes (bacteria) and the 
resulting mRNA is called a polycistronic mRNA.  Most of the mRNA created 
by prokaryotes is polycictronic.  Eukaryotic polycistronic mRNA is very 
rare.  Eukaryotic mRNAs generally represent a single gene (monocistronic 
mRNA.)

Can translation occur along a mRNA that is currently being transcribed?
Depends.  This can only occur in prokaryotes because they lack a nuclear 
membrane.  In eukaryotes, the nuclear membrane excludes ribosomes.  If 
there are no ribosomes in the nucleus, then there are no machines to 
effect translation.  In eukaryotes, translation only occurs after 
transcription is completed and the mRNA has moved out of the nucleus.

Can a single mRNA transcript act as the template for multiple ribosomes 
simultaneously?
Yes.  But remember that each ribosome can only create one protein during a 
single translation event.  The complex of a single mRNA together with many 
actively translating ribosomes is called a polysome or polyribosome.  In 
eukaryotes polysomes are only found in association with membranes.  In 
prokaryotes, polysomes are found free in the cytoplasm.

Can a single cell contain many different monocistronic mRNAs all at once?
Absolutely!  This is essential to the survival of a cell.  Many genes are 
in the process of transcription or translation or both all at the same 
time within the same cell.

Is transcription regulated?
Yes.  This regulation is very important; consider that your skin cells 
produce different proteins than your liver cells, yet they both contain 
the same DNA sequence.  This differential gene expression is acheived 
through regulation at many parts of the processes involved in protein 
production.

***

It appears to me that your question refers to the differences between 
prokaryotic and eukaryotic processes with respect to polycistronicity.  I 
will therefore expand a bit on the reanslation of polycistronic mRNA.

*PROKARYOTIC* polycistronic translation:

The bacterial site of translational initiation is an AUG sequence.  But 
this is a message to the ribosome that is already on the transcript; the 
ribosome must first bind to the transcript.  Ribosome binding occurs at an 
area called a Shine-Dalgarno sequence, which is a purine (adenine or 
guanine) rich sequence of 3-9 nucleotides which can base pair to sequences 
within the ribosomal RNA.  This lines up the ribosome to begin translation 
at the AUG start codon that is usually located 5-10 bases downstream.
In order to have translation in prokaryotes, we simply need a Shine-
Dalgerno sequence upstream of the AUG codon that is to signal 
translational initiation.  This ribosome binding  occurs rather 
infrequently without any additional help.  The mRNA must also contain 
additional helper sequences (enhancers, promoters, operators ...) which 
can be learned by studying the topic: operons.


*EUKARYOTIC* polycistronic translation:

Polycistronic translation in eukaryotes can occur by a few mechanisms.  
One way to acheive multiple proteins from a single polycistronic mRNA is 
for the first start codon (AUG) to be in a poor context for translational 
initiation.  This means that due to structural configurations of the mRNA 
(determined by mRNA sequence), some ribosomes will miss the first start 
codon and slide down the message to the second start codon, at which they 
will intitiate translation.  Remember that the ribosome binds somewhere 
upstream of the translation initiation point and slides down the 
transcript until it encounters an AUG codon.  The upstream binding of 
ribosomes is a little different in eukaryotes than it is in prokaryotes.  
Eukaryotic mRNA is usually capped at the 5' end somewhere after 
transcription but before translation (post-transcriptional mRNA 
processing) and this 5' cap binds to factors that increase the chance that 
a ribosome will attatch to the transcript in this area.  The 5' cap is 
refered to as an inverted guanosine cap and is actually a 7-methyl-
guanosine triphosphate attatched to the 5' end of the unprocessed mRNA.  
If this terminology is not yet familiar to you, ask you teacher about the 
process of translation with respect to codons or look here:
 htt
p://www.madsci.org/posts/archives/oct2000/972943713.Bc.r.html
 htt
p://www.madsci.org/posts/archives/nov2000/973721404.Cb.r.html
 htt
p://www.madsci.org/posts/archives/aug2000/965227551.Cb.r.html

And don't worry about the chemical nature of the 5' cap.  It is enough to 
know that it exists.

A second mechanism to acheive multiple proteins from a polycistronic mRNA 
is to have an internal ribosome entry site (IRES) after the first gene 
transcript but before the second gene transcript.  The ribosome will enter 
the mRNA here and slide down the transcript until it reaches an AUG codon.

A third (and not well understood) mechanism involves the enhancement of 
ribosomes binding to the mRNA downstream from a point of translational 
termination.  This is mechanistically different from the second mechanism 
because here it is the same ribosome that transcribes both gene 
transcripts, briefly hopping off the first and then back on before the 
second.  In the previous mechanism, any ribosome may enter at the IRES 
without having previously translated that particular mRNA.

***

FURTHER THOUGHTS:

Since bacterial mRNAs are mostly polycistronic, it would make sense if 
their information was arranged in this manner.  How do you think genes 
would be best be arranged to take advantage of polycistronicity?

It would be advantageous for you to read about bacterial operons.  The lac 
(lactose, a sugar) operon is very well studied and is a good place to 
start.  Here are some links.
 http://www.kean.edu
/~rkliman/BIO3705/lacoper.htm
 http://biochem.
senecac.on.ca/humphreys/lacoperon.htm

The concept of an operon was deceloped by Jacob and Monod.  If you are 
interested in the development of scientific ideas, this is a wonderful 
place to start.

After you have learned about the lac operon, read this again and try to 
understand how the lac operon fits into the bacterial model of 
polycistronicity and how it differs from the eukaryotic models.  I am sure 
you will have more question at that time, but don't despair .. that is a 
good sign.  If you have some specific questions, it means that you 
understand some parts of the model.  Self-directed learning requires the 
formulation of questions and the ability to recognise what things you 
understand and what things you do not.  It is a skill that will set you 
free on an adventure whose journey will encompase your life.  Good sailing.

***

REFERENCES:

You can find information on this an most cell biology or molecular cell 
biology textbooks.  The one I am using is "Molecular Cell Biology" by 
Lodish.  You can find this book in any university library and likely in 
your high school.  It is a bestseller.

Chris Neale
neale@innocent.com


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