www-math.bgsu.edu/~zirbel/talks/2010%20RNA_Bioinfo...

disgustedtukwilaInternet and Web Development

Dec 14, 2013 (3 years and 5 months ago)

56 views

Introduction to

RNA Bioinformatics

Craig L. Zirbel

October 5, 2010


Based on a talk originally given by Anton Petrov.

Outline

Lecture 1


Importance of RNA, examples (miRNA, riboswitches).


RNA 2D and 3D structure.


RNA structure prediction.

Lecture 2


RNA basepairs and 3D motifs


Predicting secondary structure from sequence (mfold)

Lecture 3


Statistical variability of protein and RNA sequences

ENCODE Project Consortium, Identification and
analysis of functional elements in 1% of the human
genome by the ENCODE pilot project. Nature. 2007
Jun 14447(7146):799
-
816

In the human, out of approximately 3 billion nucleotides, only about
1.5% code for proteins, although up to 93% are transcribed into RNA.
What is this “non
-
coding” RNA doing?

Mattick, J.S. (2004) The hidden genetic program of complex organisms. Scientific American 291 (4): 60
-
67.

DNA

RNA

Protein

Transcription

Translation

tRNA

Ribosomal RNA

DNA

RNA

Protein

Transcription

Translation
of exons

Reverse Transcription

Splicing

tRNA

Ribosomal RNA

Many other
types of ncRNA

Introns (RNA)

micro RNA

Mattick, J.S. (2004) The hidden genetic program of complex organisms. Scientific American 291 (4): 60
-
67.

Kim VN, MicroRNA biogenesis: coordinated cropping and dicing.
Nat Rev Mol Cell Biol.

2005 May;6(5):376
-
85

micro
RNA

Mattick, J.S. (2004) The hidden genetic program of complex organisms.
Scientific American 291 (4): 60
-
67.

Bioinformatical challenge:

given a DNA sequence,
predict microRNA genes and
their respective targets.

miRNAs in a transcript, waiting to be diced out

Peterson, K.J
., Dietrich, M.R. and McPeek, M.A. (2009)
MicroRNAs and metazoan macroevolution:

insights into canalization, complexity, and the Cambrian explosion
.

BioEssays

31:736

747.

Acquisition of novel microRNAs (shown in white boxes) may be
a driving force of recent evolution. Also a factor in cancers?

There are 84 mammal
-
specific
microRNAs, and 84 more that are
found exclusively in apes.

Montange, R. K., & Batey, R. T. (2008). Riboswitches: emerging themes in RNA structure and function. Annu Rev Biophys 37:117
-
133
.

RIBOSWITCHES

Bioinformatic
challenges:

find
riboswitches in
genomic sequences,
design novel
riboswitches.

RNAs which bind to other molecules when they are
present, altering the shape and function of the RNA.

http://
en.wikipedia.org/wiki/List_of_RNAs

Types of RNA

Bioinformatic
challenges:

Is this list
final? Could there be
more types of non
-
coding (ncRNA) that
we don’t know yet?
How to search for
novel ncRNAs in
genomes?

Goals of RNA bioinformatics


Find and classify RNA genes in genomic
sequences (using both experimental and
computational methods).


Predict secondary and 3D structure from RNA
sequence.


Infer function from structure.


Rationally design RNA molecules for
biotechnology.


Find diseases associated with RNAs (e.g., cancer
and miRNA)

Why RNA is unique



Similar to DNA in chemical composition, primary
and secondary structure, and information content,
but with more complicated structure than helices



Similar to Proteins in tertiary and 3D structure and
function,
but also very different, mostly base
-
base
interactions, fewer backbone
-
backbone



Binds substrates and catalyzes reactions, just as
proteins.



Participates in all stages of gene expression and
information transfer: transcription, splicing,
translation. Frequent target of antibiotics.



Similarities Between Protein and RNA
3D Structures


Compact folding


Hierarchical
organization


Modular domains


Specific tertiary
interactions


Molecular “mimicry”
--

Proteins that
“mimic” RNA

LIANG, H., & LANDWEBER, L. F. (2005). Molecular mimicry: Quantitative methods to study structural similarity between protein
and

RNA.

RNA, 11
(8), 1167
-
1172.

The tertiary structures of
tRNA
-
mimic translation
factors and tRNA. (
a
)
Thermus thermophilus

EF
-
G:GDP (PDB accession code
1DAR). (
b
)
Thermus
aquaticus

EF
-
Tu:GDPNP:Phe
-
tRNA
Phe

(1TTT). (
c
)
Thermus
thermophilus

RRF (1EH1). (
d
)
Yeast Phe
-
tRNA
Phe
.

RNA
s

are not linear
-

they fold back on
themselves to match up complementary strands

RNA 2D Structure Elements

Bioinformatics: sequence and genome analysis

By David W. Mount

Bioinformatic challenges:

predict most stable 2D
structures, resolve
pseudoknotted regions etc.

Basepairs are the basic units
of secondary structure.

2d to 3d structure of RNA