From: Anantharaman, Vivek (NIH/NLM/NCBI) [C]
Sent: Monday, January 23, 2006 7:58 PM
To: NLM/NCBI List ncbi-seminar
Subject: NCBI seminar Tuesday, January 24

NCBI/CBB Seminar

11:00 AM, Tuesday, January 24, 2006
Building 38A, level B2, NCBI library

Vivek Anantharaman

My talk shall contain two parts:
Part I: Toxins, RNA degradation and Post Transcriptional Gene Regulation
Dedicated RNA processing systems are found in all the 3 superkingdoms of
life and are required for maturation of tRNA, rRNA, and mRNA, and
regulating the stability of mRNA. Examples of experimentally
characterized processing complexes include the processome (degradosome)
in bacteria with several RNAses and the archaeo-euakryotic exosome, and
the eukaryotic U3 snRNP processome (4). Eukaryotes also contain several
other distinctive systems that mediate RNA processing and stability,
such as the spliceosomal particles, the nonsense-mediated mRNA decay
system, the decapping system and the micro-RNA dependent
post-transcriptional silencing apparatus. In bacteria there several
selfish mobile operons, the Toxin-Antitoxin system that maintain
themselves through novel post-segregational cell killing, that also
degrade RNA. I first show how these systems have evolved various RNA
degrading components that target mRNAs, and that the core of the
eukaryotic nonsense-mediated RNA decay system with the PIN (PilT-N)
domain nuclease has probably evolved from a post-segregational cell
killing-related system. However, the ultimate origins of the PIN domain
remained a mystery. Using sensitive sequence profile searches and
contextual information gleaned from domain architectures and predicted
operons we identify a novel family of protein domains with predicted
ribonuclease activity. These domains are found in the eukaryotic
proteins typified by the Nedd4-binding protein 1 and the bacterial
YacP-like proteins (Nedd4-BP1, YacP nucleases; NYN domains). The NYN
domain shares a common protein fold with two other previously
characterized groups of nucleases, namely the PIN (PilT N-terminal) and
FLAP/5'->3' exonuclease superfamilies. I will provide evidence that they
also share common active site containing four conserved acidic residues
with the latter two superfamilies, suggesting that they function via a
single metal catalytic mechanism rather than the previously proposed two
metal mechanism. The NYN superfamily can be traced back to LUCA and is
likely to represent one of the primary branches of the PIN-like fold(the
FLAP superfamily being the other) from which the mobile PIN subsequently
radiated. I also present evidence that the eukaryotic NYN domain
proteins represent a predicted class class of  RNA degrading enzymes
that require mono-ubiqutination for assembly into distinct nuclear
complexes.

Part II - The ISOCOT fold
Evolution of diverse catalytic and ligand-binding activities in a given
protein fold is a widely observed phenomenon in the protein-domain
universe. However, the details of this evolutionary process, general
principles, if any, and implications for origins of particular catalytic
mechanisms are poorly understood in many common protein folds. I will
explore these issues in the context of a large assemblage of
biochemically diverse protein domains sharing a common origin, namely
the sugar isomerases, translation factor eIF2B, ligand-binding domains
of the DeoR-family transcription factors, acetyl-CoA transferases and
methenyltetrahydrofolate synthetase. I will present the findings of this
study and show that whereas ligand-binding, and even generic catalytic
ability emerged early in the evolution of the fold, the specific
catalytic mechanisms appear to have independently emerged on multiple
occasions in the generic precursors of this fold. 

---------------------------------------------------------------
Vivek Anantharaman, PhD
National Center for Biotechnology Information, 
National Library of Medicine, 
National Institutes of Health, 
Bldg. 38A,Rm. N507A, 8600 Rockville pike, 
Bethesda, MD 20894, USA
Phone: (301)443-1194
Email: ananthar@mail.nih.gov