From: ncbi-seminar-admin@ncbi.nlm.nih.gov on behalf of Lakshminarayan
Iyer [lakshmin@ncbi.nlm.nih.gov]
Sent: Friday, February 21, 2003 3:02 PM
To: ncbi-seminar@ncbi.nlm.nih.gov
Subject: Seminar Tuesday, Feb 25, 11 AM.

Tuesday, Feb 25, 11 AM
5th floor conference room, Bldg. 38A

Lakshminarayan M Iyer

Computational Biology Branch, National Center for Biotechnology
Information,
NLM, NIH

The Evolutionary histories of the DNA dependent RNA polymerase and
eukaryotic RNA dependent RNA polymerase and the multidomain
nature of the DNA dependent RNA polymerase

The eukaryotic RNA-dependent RNA polymerase (RDRP) is involved in the
amplification of regulatory microRNAs during post-transcriptional gene
silencing. The origins of this eukaryote-specific polymerase remains a
mystery. Using extensive sequence profile searches,we identified
bacteriophage homologs of the eukaryotic RDRP. Further, detailed
sequence comparison, aided by examination of the crystal structure of
the cellular DNA-dependent RNA polymerase (DDRP), showed that the RDRP
and the beta prime subunit of DDRP (and its orthologs in archaea and
eukaryotes) contain a conserved double-psi beta-barrel (DPBB) domain and
share a common mechanism of catalysis. Structure analysis revealed that
in addition to the beta prime subunit, the beta subunit of DDRP also
contains a distorted DPBB domain. The DPBB domains of the two DDRP
subunits together form the catalytic cleft,with the domain from the beta
and beta prime subunits supplying different charged residues that are
involved in catalysis. We hypothesize that the ultimate ancestor of
these RNA polymerases functioned as a homodimer of a generic,
RNA-binding DPBB domain. and served as a cofactor for a ribozyme RNA
polymerase. Subsequent evolution of DDRP involved accretion of distinct
sets of additional domains that were uncovered as a result of the study.
In the DDRPs, these included a Zn-ribbon, an AT-hook-like module and a
sandwich-barrel hybrid motif (SBHM) domain. Further, lineage-specific
accretion of SBHM domains and other, DDRP-specific domains were observed
in bacterial DDRPs. In contrast, the archaeo-eukaryotic DDRPs seem to
have acquired a different set of domains such as a RRM domain, a
four-stranded alpha + beta domain that is shared with the alpha subunit
of DDRP, and a beta grasp domain. These results and the evolutionary
implications thereof will be discussed.

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-- 
Lakshminarayan Iyer
NCBI, NIH,
Bethesda, MD-20894
Tel : 301-594-7090 (Work)
      : 301-530-1348 (Home)