interspersed sequences

Graham Dellaire dellaire at odyssee.net
Sun Feb 16 17:29:12 EST 1997


Alain Bernot Wrote:
 
 > hi
 > 
 > can anybody tell me if the interspersed sequences in the murine genome
 >are related to a known gene (in the same way as the human Alu is related
to
 >the 7SL RNA in primates). I am also looking for articles about repeated
sequences
 >in non-human species.
  
 > thanks
  
Dear Alain,

I am not sure if you mean Alu's (B1 in mouse) or Line's (Lmd1 in mouse) or
both. But our lab has worked with recombination extensively with Line
sequences
in mouse, rat and human cell lines.  Line sequences contain two open
reading frames.  Orf1 has DNA binding activity and ORF2 has both
endonuclease and RTase activity.  The RTase is much like the RTase of HIV
and other retroviruses. Lines characteristicly lack LTR's (unlike retro
viral genomes), are AT rich and contain a poly A tail.  Most lines
interestingly are found in G bands and Alu's are found in R bands (being GC
rich).  There are 100,000 lines in the genome and about 97% are truncated
at the 5' end.  Only about 3,000 are full length.  Few of the 3,000 full
length copies are believed to be functional.  Perhaps only a few exist. 
Candidates have been recently isolated from Line integrations in the Factor
VIII gene (L!.2) and from the  dystrophin gene (LRE2).  Active lines are
thought to be expressed during gametogenesis and or during development as
germline transmission would require this (also LINE transcripts are found
in EC and ES cells).

The prototypical line is about 6 kb long and looks sort of like this:

5' UTR    ORF1                   ORF2                3' UTR       polyA
 ------------|--------------------|-------------------------------|---------
-
 |           |  DBD            |Endo|      RT       | C |        |AAAAAAAA
 ------------|--------------------|-------------------------------|---------
-
 
Where DBD=Dna binding domain
           Endo=endonuclease
           RT=reverse transcriptase
           C= cystein rich domain (function??)
The 5' UTR contains an internal promoter (rnapol II and III)

The DBD, endonuclease domain and RTase are required for retrotransposition
and the cysteine rich domain may have a function in this process too.

There are theories that Lines may have originated from a parasitic
infection by a fungi.  (see Aksoy et al. 1990 for abstract go to 
 http://www3.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=90192150&form=6&db
=
 m&Dopt=b )
 
Interestingly this is also a theory for the RAG-1 and RAG-2 genes that are
required for VDJ recombination (and thus anti-body diversity) in mammals. 
They are convergently transcribed in opposite sense to each other.  

For a phylogenic history of lines in rodents see: W.S Modi (1996) Mol. Biol
Env.
 http://www3.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=96212984&form=6&db
=m&Dopt=b
 
Or
 A. V. Furano & K. Usdin (1995) J. Biol. Chem
 
http://www3.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=96029598&form=6&db=

m&Dopt=b

Also look up in medline the following author's 
 
Belmaaza A. 
Chartrand P.
Jurka J.
Casavant N.C.
Singer M.F.
 
Hope this helps
 

Graham Dellaire
Moderator
 



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