Biomol

Science Webinar Series
Noncoding RNAs:
22 October, 2008
A New Paradigm for Gene Regulation
Brought to you by the Science/AAAS Business Office

Participating Experts:
George Calin, M.D./Ph.D. The University of Texas M.D. Anderson Cancer Center Houston, Texas Joshua Mendell, M.D./Ph.D. Institute of Genetic Medicine Johns Hopkins University Baltimore, Maryland

Sponsored by:Non-codingRNAs: from scientist benchside to patient bedside
George Adrian Calin, MD, PhD
Associate Professor Experimental Therapeutics Dept Univ. Texas, MD Anderson CC Houston, US

WHY NONCODING RNAS MAKE SUCH A BIG SPLASH IN BIOLOGY AND MEDICINE?

A non-codingRNA revolution in the cancer society
D13S273 D13S1168 D13S1150 D13S319 D13S272

Centromere

Telomere

0

100

200

300

400500

600

700

1500 Kb

13q14.3 in CLL

deleted region in CLL, MM Pr Ca, Pit Ad

NY-REN-34 antigen

KPNA3

CLLD6

LEU 5

KCNRG CLLD8 CLLD7 ARLTS1

Non-coding RNAs (ncRNAs) Protein coding genes (PCGs)

(Calin et al, PNAS, 2002; Calin et al, N Engl J Med, 2005a; Calin et al, N Engl J Med 2005b)

A non-codingRNA revolution in the cancer society
D13S273 D13S1168 D13S1150D13S319 D13S272

Centromere

Telomere

0

100

200

300

400

500

600

700

1500 Kb

13q14.3 in CLL

deleted region in CLL, MM Pr Ca, Pit Ad

NY-REN-34 antigen

KPNA3

CLLD6

LEU 5

LEU 1 LEU 2

DLEU 7

KCNRG CLLD8 CLLD7 ARLTS1

miR16-1 miR15-a

Non-coding RNAs (ncRNAs) Protein coding genes (PCGs)

(Calin et al, PNAS, 2002; Calin et al, N Engl J Med,2005a; Calin et al, N Engl J Med 2005b)

WHAT ARE THE NONCODING RNAS?

The non-codingRNA dictionary of the human genome
60-70% of the human genome is transcribed, while the total fraction of bases occupied by known PCGS is only about 2%
(Mattick & Makunin, Hum Mol Genet 2006) Makunin,

The non-codingRNA dictionary of the human genome
60-70% of the human genome is transcribed, while thetotal fraction of bases occupied by known PCGS is only about 2%
(Mattick & Makunin, Hum Mol Genet 2006) Makunin,
NAME
tRNAs (transfer RNA) tmRNA (transfer messanger RNA) rRNA

FUNCTION
Translation of genetic information. Trans translation. Ribosome component, catalysis of peptide bound formation. Pre-mRNA splicing, telomerase maintenance; part of snRNPs (small nuclear ribonucleoproteins).RNA biogenesis; pseudourydylation. RNA modifications like 2’-O-methylation and

REFERENCEs

(Wower, Wower et al. 20 08)

HOUSKEEPING RNAs

snRNA (Small nuclear RNA) snoRNA (Small nucleolar RNA) Telomerase RNA FC RNA Centromeric repeat derived RNA RNase P RNase MRP Antisense-RNA

(Barrandon, 2008)

Spiluttini

et

al.

(Filipowicz and Pogacic 2002) (Theimer and Feigon 2006)(Kettenberger, Eisenfuhr et al. 2006) (Chen, Zhang et al. 2008) (Jarrous and Reiner 2007) (Martin and Li 2007) (Amaral, Dinger et al. 2008) (Yang and Kuroda 2007) (Rinn, Kertesz et al. 2007) (Heard and Disteche 2006) (Kent and Mendell 2006) (Buhler and Moazed 2007) (Aravin, Gaidatzis et al. 2006; Brower-Toland, Findley et al. 2007) (Barrandon, Spiluttini et al. 2008)

Telomeric DNA synthesis. Directinhibition of RNA Polymerase II and RNA transcription Kinetochore assembly and chromosome segregation. Rybozymes that participate in tRNA processing. RNase mitochondrial RNA; biogenesis of ribosomes. Regulation of gene expression in CIS or in TRANS either at the D NA or mRNA level Dosage Compensation and genomic imprintin; epigenetic control of development trajectories (HOTAIR); X-chromosomeinactivation (XIST and TSIX ) Mainly post-transcriptional regulation of gene expression.

REGULATORY RNAs

LONG ncRNA miRNA piRNAs (PIWI interacting RNAs) Protein function modulators

Eterochromatin formation via RNAi pathways; Role in gametogenesis.

6S RNA, SRA RNA (steroid receptor RNA activator).

Small RNAs make big splash
Cytoplasm
Genome - miRNA gene

Pri-miRNA

Nucleus

Drosha...