BIOINFORMATICS REVIEW- AUGUST 2016

Aug 2016 VOL 2 ISSUE 8

“Research is what I'm doing when I don't know what I'm doing.”

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Wernher von Braun

The Microbe Story at ASM microbe 2016-Need for Microbiome Research

miRNA targets and their functions

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Contents

August 2016

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Topics Editorial....

03 Transcriptomics miRNA targets and their functions

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04 Bioinformatics News The Microbe Story at ASM microbe 2016Need for Microbiome Research 08

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EDITOR Dr. PRASHANT PANT FOUNDER TARIQ ABDULLAH EDITORIAL EXECUTIVE EDITOR TARIQ ABDULLAH FOUNDING EDITOR MUNIBA FAIZA SECTION EDITORS FOZAIL AHMAD ALTAF ABDUL KALAM MANISH KUMAR MISHRA SANJAY KUMAR PRAKASH JHA NABAJIT DAS REPRINTS AND PERMISSIONS You must have permission before reproducing any material from Bioinformatics Review. Send E-mail requests to info@bioinformaticsreview.com. Please include contact detail in your message.

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PUBLICATION INFORMATION Volume 1, Number 1, Bioinformatics Reviewâ„¢ is published quarterly for one year (4 issues) by Social and Educational Welfare Association (SEWA)trust (Registered under Trust Act 1882). Copyright 2015 Sewa Trust. All rights reserved. Bioinformatics Review is a trademark of Idea Quotient Labs and used under license by SEWA trust. Published in India

EDITORIAL: Welcoming BiR in its 2nd year

EDITORIAL

Bioinformatics, being one of the best field in terms of future prospect, lacks one thing - a news source. For there are a lot of journals publishing a large number of quality research on a variety of topics such as genome analysis, algorithms, sequence analysis etc., they merely get any notice in the popular press.

Dr. Prashant Pant

Editor

One reason behind this, rather disturbing trend, is that there are very few people who can successfully read a research paper and make a news out of it. Plus, the bioinformatics community has not been yet introduced to research reporting. These factors are common to every relatively new (and rising) discipline such as bioinformatics.

Although there are a number of science reporting websites and portals, very few accept entries from their audience, which is expected to have expertise in some or the other field.

Bioinformatics Review has been conceptualized to address all these concerns. We will provide an insight into the bioinformatics - as an industry and as a research discipline. We will post new developments in bioinformatics, latest research.

We will also accept entries from our audience and if possible, we will also award them. To create an ecosystem of bioinformatics research reporting, we will engage all kind of people involved in bioinformatics - Students, professors, instructors and industries. We will also provide a free job listing service for anyone who can benefit out of it.

Letters and responses: info@bioinformaticsreview.com

TRANSCRIPTOMICS

miRNA targets and their functions

Image Credit: Google Images

“This article highlights the targets and functions of the miRNAs. Identification of the target and the functions of the miRNAs is essential for their target prediction which will be covered in upcoming articles.”

m

iRNA

Targets

The regulatory RNA molecules microRNA or miRNA binds to the mRNA through complementary base pairing irrespective of complete or incomplete binding.

Recent studies have revealed that miRNAs specifically bind to the 3’UTRs of the target mRNA possessing either of the two binding patterns [1]. There are two classes of binding patterns [1]: 1. One class of pattern consists of perfect Watson-Crick binding at the 5’-end of the miRNA. This region is known as “seed-region” and found at the 2-7 base of the miRNA. This region is able to suppress the target mRNAs without having a complete base

pairing at the 3’-end of the miRNA. 2. Another class involves the improper complementary base pairing at the 5’-end of the miRNAs, but to overcome this imperfect pairing, there are some additional base pairings at the 3’-end of the miRNA. An mRNA can have multiple sites for a miRNA and also several miRNAs can bind to a single mRNA [2]. This kind of relation between mRNA and miRNA make the miRNA regulatory mechanism more complex [2]. miRNA Functions Some studies have revealed that there are some miRNA intermediate duplexes which may have bulges within its one of the strands due to the inappropriate binding and

mismatches [3]. These elements unwind the duplex and interfere in the silencing process [4]. There is some evidence indicating about controlling miRNA at the post-transcriptional level as the maturation of miRNA involves several steps which may be regulated [7,8,9]. It has been suggested from few studies that the expression of those miRNAs which originate from the introns of genes are transcribed along with the host genes [10-12,13], and is coupled with their host genes [14,15]. miRNAs in animals binds to the translational receptors partially to the 3’-UTR of the regulatory elements of the transcripts [16], without affecting the functions of the target sites and the 5’-UTR [17,18]. Another major silencing event of miRNAs destabilizes the target mRNAs and effect at the transcript level [19,20]. Some studies Bioinformatics Review | 6

reveal that the miRNAs may have positive or negative regulatory effects [21]. Some evidence shows that under some conditions in some specific cell types, miRNAs can enhance translation [22]. miRNAs regulate the mRNAs and the RNAs and nothing seems to prevent this regulation [4]. It has been illustrated in a study done with Arabidopsis thaliana that miRNAs may bind to the pseudo targets in other non-coding RNAs to negatively regulate the miRNA activity [23].

There are many problems with the miRNA world which can be solved computationally, among which the miRNA target prediction is the essential one, as the function of miRNA depends on its target, therefore, in the cases of diseases such as cancer, it becomes necessary to predict the targets of miRNAs. We will discuss the most common features of algorithms and tools for the miRNA target prediction in the upcoming articles.

References 1.

Rajewsky N. microRNA target predictions in animals. Nat Genet 2006;38:S8–13.

2.

Bing Liu, Jiuyong Li, and Murray J. Cairns. Identifying miRNAs, targets and functions. Briefings in Bioinformatics. page 119; doi:10.1093/bib/bbs075.

3.

Khvorova,A., Reynolds,A. and Jayasena,S.D. (2003). Functional siRNAs and miRNAs exhibit

strand bias. Cell, 115,209–216Khvorova,A., Reynolds,A. and Jayasena,S.D. (2003).Functional siRNAs and miRNAs exhibit strand bias. Cell, 115, 209–216.

4.

5.

6.

D. Mendes, A. T. Freitas and M.-F. Sagot.

Current tools for the identification of miRNA genes and their targets. Nucleic Acids Research, 2009, Vol. 37, No. 8 2419– 2433.doi:10.1093/nar/gkp145.

Park,M.Y., Wu,G., Gonzalez-Sulser,A., Vaucheret,H. and Poethig,R.S. (2005) Nuclear processing and export of microRNAs in Arabidopsis. Proc. Natl Acad. Sci. USA, 102, 3691–3696.

Bartel,D.P. (2004) MicroRNAs: genomics, biogenesis, mechanism,and function. Cell, 116, 281–297.

7.

Cullen,B.R. (2004) Transcription and processing of human microRNA precursors.

Mol. Cell, 16, 861–865.

8.

Ambros,V., Lee,R.C., Lavanway,A., Williams,P.T. and Jewell,D.(2003) MicroRNAs and other tiny endogenous RNAs in C. elegans.Biol., 13, 807–818.

9.

Luciano,D.J., Mirsky,H., Vendetti,N.J. and Maas,S. (2004) RNA editing of a miRNAprecursor. RNA, 10, 1174–1177.

10. Lim,L.P., Lau,N.C., Weinstein,E.G., Abdelhakim,A., Yekta,S.,Rhoades,M.W., Burge,C.B. and Bartel,D.P. (2003) The microRNAs of Caenorhabditis elegans. Genes Dev., 17, 991–1008.

11. Lai,E.C., Tomancak,P., Williams,R.W. and Rubin,G.M. (2003) Computational identification of Drosophila microRNA genes.Genome Biol., 4, R42.

12. Rodriguez,A., Griffiths-Jones,S., Ashurst,J.L. and Bradley,A. (2004) Identification of mammalian microRNA host genes and transcription units. Genome Res., 14, 1902– 1910.

13. Ying,S.-Y. and Lin,S.-L. (2005) Intronic microRNAs. Biochem.Res. Commun., 326, 515–520.

14. Baskerville,S. and Bartel,D.P. (2005) Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA, 11, 241–247.

15. Bartel,D.P. (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116, 281–297.

16. Lai,E.C. (2002) Micro RNAs are complementary to 3’ UTR sequence motifs that mediate negative post-transcriptional regulation. Nat. Genet., 30, 363–364.

17. Kloosterman,W.P., Wienholds,E., Ketting,R.F. and Plasterk,R.H.A. (2004) Substrate requirements for let-7 function in the developing zebrafish embryo. Nucleic Acids Res., 32, 6284–6291.

18. Lytle,J.R., Yario,T.A. and Steitz,J.A. (2007) Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5’ UTR as in the 3’ UTR. Proc. Natl Acad. Sci. USA, 104, 9667– 9672.

19. Lim,L.P., Lau,N.C., Garrett-Engele,P., Grimson,A., Schelter,J.M., Castle,J., Bartel,D.P., Linsley,P.S. and Johnson,J.M. (2005) Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature, 433, 769–773.

20. Pillai,R.S. (2005) MicroRNA function: multiple mechanisms for a tiny RNA? RNA, 11, 1753– 1761.

21. Ambros,V. (2001) microRNAs: tiny regulators with great potential.Cell, 107, 823–826.

22. Vasudevan,S., Tong,Y. and Steitz,J.A. (2007) Switching from repression to activation: microRNAs can up-regulate translation.Science, 318, 1931–1934.

23. Chitwood,D.H., and Timmermans,M.C.P. (2007) Target mimics modulate miRNAs. Nat. Genet., 39, 935–936.

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BIOINFORMATICS NEWS

The Microbe Story at ASM microbe 2016Need for Microbiome Research Image Credit: Stock Photos

“The tech mogul championed the cause for prevention and cure for several infectious diseases across the globe, especially in developing countries.”

T

he 2016 American Society for Microbiology-Microbe (ASM Microbe 2016) was an August meeting held in the magnificent city of Boston at the Boston Convention and Exhibition Center (BCEC) and its high-traffic neighborhood from June 16-20. It is the first time that the ASM general meeting and the ICAAC (Interscience Conference On Antimicrobial Agents And Chemotherapy) merged to make a single giant convention.

This year the meeting saw huge participation from academia, the pharmaceutical industry, and several biotechs. There were big brands as well as smaller start-ups in the microbial horizon clamoring for

attention amongst the 7000-odd attendees. Indeed, in the words of David C. Hooper, MD; Massachusetts General Hospital and Chair, ASM Meetings Board-“It’s really the only meeting of its kind. It covers the scope of microbiology and microbial sciences from A to Z, from basic to clinical applications”. The event kickstarted with a Conversation with Bill Gates: Bringing the Frontiers of Science to the Front Lines of Development that rightfully set the tone for the rest of the conference.

The tech mogul championed the cause for prevention and cure for several infectious diseases across the globe, especially in developing countries. He highlighted the need for more microbe-oriented research

to eradicate the infectious diseases.

menace

of

The main event was divided into several parallels running scientific tracks and workshops conducted by experts in the field. From the pharma standpoint, sessions that focused on host-microbe ecology, the translational aspect of microbial research and therapeutics and prevention were my top choices.

Clostridium difficile infection, HIV cure, dysbiosis and rebiosis, fecal matter transplant, prebiotics and probiotics, microbiome interaction, inflammation were some of the buzzwords from these sessions. It is perhaps not out of context to mention that my work on the discovery of microbial metabolite Bioinformatics Review | 8

mimics was very well received and had the floor cheering. GSK’s unique approach towards ‘Microbiome-toTargets’ was lauded at all levels.

Several stalwarts in the field of microbiome research like Robert Knight (University of California, San Diego), Peter Turnbaugh (University of California, San Francisco), Andrew Goodman (Yale University), Laurie E. Comstock (Harvard University), were also present in the audience. I had an opportunity to a have a talk on my research work which featured in the “Influence of Microbial Products on the Gut Microbiota or Host” symposium.

The wealth of information amassed from the Human Microbiome Project (http://hmpdacc.org/) needs processing, in-depth analysis, development of new Bioinformatics

tools and software to meaningfully interpret the microbiome association in human health and their clinical implications.

Sequencing of the 16S rRNA regions from the commensal microbes bypassed the challenges of identifying bacteria from cultures (most of the commensals from different body sites are actually still uncultivable in the lab). At ASM, scientists from various disciplines were unequivocal in stressing the need for more microbiome research given the intricate biology of hostmicrobe interaction. Understanding the molecular mechanism of this “cross-talk” is still in its infancy, emphasizing the need for more pharma investment in this area to develop new therapeutic products.

As increasing number of evidence points to the involvement of the commensal microbiota in several

autoimmune disorders, metabolic diseases, respiratory diseases, and neurological disorders, it is only logical to study bugs that are our “buddies” as well as the ones that are “baddies”. In conclusion, the microbiome market will only gain traction in near future.

Somdutta Saha, Ph.D. Early Talent Postdoctoral fellow, Computational Biology, R&D, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville. Pennsylvania 19426.

Disclaimer: The views expressed in this article are that of the author’s alone and not necessarily endorsed by GlaxoSmithKline(GSK) Plc.

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