INTERFERENCE means the act of interfering with something, here, with RNA. RNAi is an evolutionarily conserved mechanism triggered by dsRNA molecules, to prevent the expression of specific genes or the translation, causes sequence-specific degradation of the targeted mRNA molecules of that particular gene. It was also known as CO-SUPPRESSION, POST TRANSCRIPTIONAL GENE SILENCING [PTGS] in plants and QUELLING in fungi.
RNA interference (RNAi) is a mechanism that inhibits gene expression at the stage of translation or by hindering the transcription of specific genes.
RNAi targets include RNA from viruses and transposons.
RNAi is a powerful, conserved biological process through which the small, double-stranded RNAs specifically silence the expression of homologous genes, largely through degradation of their cognate mRNA.
RNA interference (RNAi) is a biological process in which RNA molecules inhibit gene expression, typically by causing the destruction of specific mRNA molecules. Historically, it was known by other names, including co-suppression, post-transcriptional gene silencing (PTGS), and quelling.
RNA interference (RNAi) is a mechanism that inhibits gene expression at the stage of translation or by hindering the transcription of specific genes.
RNAi targets include RNA from viruses and transposons.
RNAi is a powerful, conserved biological process through which the small, double-stranded RNAs specifically silence the expression of homologous genes, largely through degradation of their cognate mRNA.
RNA interference (RNAi) is a biological process in which RNA molecules inhibit gene expression, typically by causing the destruction of specific mRNA molecules. Historically, it was known by other names, including co-suppression, post-transcriptional gene silencing (PTGS), and quelling.
RNA interference (RNAi): Cellular process by which an mRNA is targeted for degradation by a dsRNA with a strand complementary to a fragment of such mRNA.
DNA and RNA Structure
Central Dogma of Life
Protein Engineering (Brief)
Introduction to microRNA (miRNA)
History of miRNA
Biogenesis of miRNA
Conservation of miRNA
Impact of miRNA
miRNA Therapy
Conclusion
RNA interference (RNAi): Cellular process by which an mRNA is targeted for degradation by a dsRNA with a strand complementary to a fragment of such mRNA.
DNA and RNA Structure
Central Dogma of Life
Protein Engineering (Brief)
Introduction to microRNA (miRNA)
History of miRNA
Biogenesis of miRNA
Conservation of miRNA
Impact of miRNA
miRNA Therapy
Conclusion
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
RNA interference (RNAi) is a system within living cells that takes part in controlling which genes are active and how active they are. RNA interference has an important role in defending cells against parasitic genes – viruses and transposons – but also in directing development as well as gene expression in general.
RNA interference (RNAi) is a biological process in which RNA molecules inhibit gene expression, typically by causing the destruction of specific mRNA molecules. Two types of small ribonucleic acid (RNA) molecules – microRNA (miRNA) and small interfering RNA (siRNA) – are central to RNA interference.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
RNA interference (RNAi) is a biological process in which RNA molecules inhibit gene expression, typically by causing the destruction of specific mRNA molecules. Historically, it was known by other names, including co-suppression, post-transcriptional gene silencing (PTGS), and quelling. Only after these apparently unrelated processes were fully understood did it become clear that they all described the RNAi phenomenon. Andrew Fire and Craig C. Mello shared the 2006 Nobel Prize in Physiology or Medicine for their work on RNA interference in the nematode worm Caenorhabditis elegans, which they published in 1998. Since the discovery of RNAi and its regulatory potentials, it has become evident that RNAi has immense potential in suppression of desired genes. RNAi is now known as precise, efficient, stable and better than antisense technology for gene suppression. Two types of small ribonucleic acid (RNA) molecules – microRNA (miRNA) and small interfering RNA (siRNA) – are central to RNA interference. RNAs are the direct products of genes, and these small RNAs can bind to other specific messenger RNA (mRNA) molecules and either increase or decrease their activity, for example by preventing an mRNA from producing a protein. RNA interference has an important role in defending cells against parasitic nucleotide sequences – viruses and transposons. It also influences development.
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
This pdf is about the Schizophrenia.
For more details visit on YouTube; @SELF-EXPLANATORY;
https://www.youtube.com/channel/UCAiarMZDNhe1A3Rnpr_WkzA/videos
Thanks...!
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
The increased availability of biomedical data, particularly in the public domain, offers the opportunity to better understand human health and to develop effective therapeutics for a wide range of unmet medical needs. However, data scientists remain stymied by the fact that data remain hard to find and to productively reuse because data and their metadata i) are wholly inaccessible, ii) are in non-standard or incompatible representations, iii) do not conform to community standards, and iv) have unclear or highly restricted terms and conditions that preclude legitimate reuse. These limitations require a rethink on data can be made machine and AI-ready - the key motivation behind the FAIR Guiding Principles. Concurrently, while recent efforts have explored the use of deep learning to fuse disparate data into predictive models for a wide range of biomedical applications, these models often fail even when the correct answer is already known, and fail to explain individual predictions in terms that data scientists can appreciate. These limitations suggest that new methods to produce practical artificial intelligence are still needed.
In this talk, I will discuss our work in (1) building an integrative knowledge infrastructure to prepare FAIR and "AI-ready" data and services along with (2) neurosymbolic AI methods to improve the quality of predictions and to generate plausible explanations. Attention is given to standards, platforms, and methods to wrangle knowledge into simple, but effective semantic and latent representations, and to make these available into standards-compliant and discoverable interfaces that can be used in model building, validation, and explanation. Our work, and those of others in the field, creates a baseline for building trustworthy and easy to deploy AI models in biomedicine.
Bio
Dr. Michel Dumontier is the Distinguished Professor of Data Science at Maastricht University, founder and executive director of the Institute of Data Science, and co-founder of the FAIR (Findable, Accessible, Interoperable and Reusable) data principles. His research explores socio-technological approaches for responsible discovery science, which includes collaborative multi-modal knowledge graphs, privacy-preserving distributed data mining, and AI methods for drug discovery and personalized medicine. His work is supported through the Dutch National Research Agenda, the Netherlands Organisation for Scientific Research, Horizon Europe, the European Open Science Cloud, the US National Institutes of Health, and a Marie-Curie Innovative Training Network. He is the editor-in-chief for the journal Data Science and is internationally recognized for his contributions in bioinformatics, biomedical informatics, and semantic technologies including ontologies and linked data.
2. WHAT IS RNA INTERFERENCE ?
INTERFERENCE means the act of interfering with something,
here, with RNA.
RNAi is an evolutionarily conserved mechanism triggered by dsRNA
molecules, to prevent the expression of specific genes or the
translation, causes sequence specific degradation of the targeted
mRNA molecules of that particular gene.
[ mRNA carry a genetic code identical to that of dsRNA]
It was also known as CO-SUPPRESSION, POST
TRANSCRIPTIONAL GENE SILENCING [ PTGS] in plants and
QUELLING in fungi.
5. DISCOVERY OF RNAi
It was first discovered in 1998 by ANDREW FIRE
and CRAIG C. MELLO and they shared THE 2006
NOBEL PRIZE in PHYSIOLOGY OR MEDICINE for
their work on RNA interference in the Nematode
worm Caenorhabditis elegans, which they published
in the journal NATURE on February 19, 1998.
6. 1. Injecting the mRNA encoding muscle protein
No change in the behaviour of worm
2. Injecting the antisense sequence of mRNA which can pair with mRNA
encoding muscle protein
Worm displayed peculiar twitching movements, similar movements were seen
when worm is completely locked that muscle protein
3. Injected the sense and antisense RNA together as double strand
7. RNAi is specific for the gene whose mRNA code matches that of
injected RNA molecules.
RNAi can spread between cells and even be inherited.
It is enough to inject tiny amount of dsRNA to achieve an effect.
The effect is non stoichiometric, small amount of dsRNA can wipe
out the excess amount of mRNA.
dsRNA needs to be directed against an exon, not an intron in order
to be effective.
RNAi is a catalytic process.
NEED FOR INTERFERENCE –
1. Defence mechanism- It has an important role in defending cells
against parasitic nucleotide sequences [ viruses and transposon ] .
2. Genome wide regulation- RNAi plays a role in regulating the
development and genome maintenance.
8.
9. Generally RNA is a single stranded molecule. What ever is there in side
the cell [ endogenous] if there is by any chance they produce a double
stranded RNA this lead to the formation of
(1) micro RNA (miRNA)
(2) short hairpin RNA (shRNA)
(3) small interfering RNA (siRNA)
ds RNAs are produced by – transcription of inverted repeats, viral
replication, transcription of RNA by RNA dependent RNA polymerase(Rd
Rp).
PTGS defective plants are more sensitive to infection by RNA viruses.
In RNAi defective nematodes, transposons are much more actives.
ds RNA lead to the silencing of the actual protein coding mRNA. This is
called RNA mediated gene silencing and they bring out the gene silencing
process by combining many other proteins together like RISC [RNA
induced silencing complex ] and Dicer.
10. RISC [RNA induced silencing complex]
RISC breakdown the mRNA into smaller
fragments so that protein synthesis is
not possible .
RISC complex contains ARGONAUTE 2
[AGO 2] protein.
This AGO2 contains 2 domains.
1. PIWI- the PIWI domain is a
conserved domain inside the Argonaute
family. The C- terminal of this domain
required for Endonuclease.
2. PAZ- it is also a conserved domain
inside this Argonaute family. It is
located near the center of the AGO2
proteins and provides grooves substrate
binding.
Argonaute is also a RNAse H type of
enzyme.
11. There is another one type of enzyme DICER, which is a
RNAse III type of enzyme.
It is a ds RNA specific endonuclease enzyme which
specifically binds to ds RNA and break down it to form
siRNA, shRNA and miRNA.
Processive ATP dependent enzyme- no larger intermediate.
These proteins contain an amino terminal helicase domain,
dual RNAse III domain in the carboxy terminal segment and
ds RNA binding motifs.
Dicer homologs exist in many organisms including C. elegans,
drosophila, yeast and human.
Loss of Dicer- loss of silencing
DICER
12. One molecule of the Dicer protein,
which catalyzes the cleavage of dsRNA
to siRNAs. The RNase III domains are
colored green, the PAZ domain yellow,
the platform domain red, and the
connector helix blue.
16. MECHANISM OF mi RNA INTERFERENCE
Long ssRNA [ sequence complementarity ] which
form dsRNA of stem loop structure, also called
Pri mi RNA.
Pri mi RNA is cut by Drosha and DGCR8, then
form pre mi RNA, which is transported to the
cytoplasm by transmembrane protien exportin.
Dicer break down the pre mi RNA to the mi RNA
duplex, which has 2 nucleotide over hangs at 3’
ends and 5’ mono phosphate region.
RISC is attached and released a strand, called
passenger strand and the guide strand with RISC
[ miRNA complex active] paired with the target
mRNA and breaks it down.
17. MECHANISM OF shRNA INTERFERENCE
Short hairpin
structured
RNA formed
by RNA self
comlementari
ty in
endogenous
process or
artificial
injection or
via virus
attack
shRNA
formation
by the
processing
of Dicer
shRNA
ready to
attach
with RISC
By the
activity of
slicer and
argonaute,
passenger
strand
separate
from the
guide
strand of
sh RNA
Guide
strand of
shRNA has
compleme
ntarity
with a
mRNA.
Bind to
that
mRNA.
mRNA
breaks
down and
degraded.
Translation
blocks. No
protein
formation.
18. MECHANISM OF siRNA INTERFERENCE
si RNA play an important role in RNA interference.
They are mediators and indicators of PTGS [ post
transcriptional gene silencing]
21- 25 nucleotides fragments, which bind to the
complementary portion of the target mRNA and tag it
for degradation.
A single base pair difference between the siRNA and
the target mRNA is enough to block the process.
Each strand of si RNA has 5’ phosphate termini, 3’
hydroxyl termini, 2/3 nucleotide at 3’ overhang.
19.
20. Once the process is done this break down components of
mRNA has 3 important features.
1. they may have some complementarity with guide RNA
then by binding to it they may became again dsRNA then
RNA interference again start.
2. they may be degraded by cellular enzyme.
3. they may be pair with other RNA then again RNA
interference amplified.
21. APPLICATION OF RNA INTERFERENCE
A systemic way to immunize an organism against the invasive nucleic
acids from viruses and transposons via inducing the RNAi responses.
Virus induced gene silencing ( VIGS ) in plants is accomplished by RNAi.
Many plant viruses code for viral suppressor of gene silencing ( VSGS ).
VSGS acts as a virulence determinant, and hence, is required for
developing anti virulence response in the host. The host can also modify
its PTGS/RNAi mechanism to prevent future infection.
RNAi may target DNA virus amplification in plants.
Plays a crucial role in the development process of multicellular
organisms.
DNA vector mediated RNAi silencing genes transiently in mammalian
cells, while other expression systems are used for stable silencing.
Oncogene which accelerate cancer growth, can be targeted by RNAi.
22. TIME LINE :
YEAR DISCOVERIES
1990 CO SUPPRESSION OF PURPLE COLOURING PLANTS
1998 dsRNA INJECTION IN WORMS, RNAi DISCOVERED
1999 SHORT RNAs IDENTIFIED IN PLANTS, RNAi SHOWN IN VITRO
2000 RISC ACTIVITY IS PARTIALLY PURIFIED
2001 SiRNAs IDENTIFIED, DICER IDENTIFIED
2002 RNAi USED AGAINST HIV, GENOME WIDE RNAi SCREENS BEGIN
2003 EXPLORING PLANT GENOMES BY RNA INDUCED GENE SILENCING
23. TIME LINE:
YEAR DISCOVERIES
2003 EXPLORING PLANT GENOMES BY RNA INDUCED GENE SILENCING
2004 INDUCTION OF DNA METHYLATION AND GENE SILENCING BY SHORT
INTERFERRING RNAS IN HUMAN CELLS
2005 PLANT NUCLEAR RNA POLYMERASE IV MEDIATES siRNA AND DNA
METHYLATION
2006 miRNAs CAN FUNCTION AS TUMOR SUPPRESSORS AND ONCHOGENES,
SPECIFIC EFFECTS OF miRNAs ON THE PLANT TRANSCRIPTOME
2010 EVIDENCE OF RNAi IN HUMANS FROM SYSTEMICALLY ADMINISTERED
siRNA VIA TARGETED NANOPARTICLES
2015 MODULATING THE TUMOR MICROENVIRONMENT WITH RNAi AS A
CANCER TREATMENT STRATEGY
2016 RNAi TARGETING ETS-1 DOWNREGULATES RRM2 AND ENHANCES
GEMCITABINE SENSITIVITY IN PANCREATIC CANCER CELLS
24. FUTURE PERSPECTIVE
First progress in RNAi technology has shown promise for use in
reverse genetics and therapy.
However, mechanistic complexities of this technology still need to be
determined.
A revolutionary tool for functional genomics in organisms.
Multiple studies have defined the role of RNAi in mammalian and
plant defence systems.
A plethora of studies have utilized RNAi technology to modulate gene
expression.
RNAi based full genomic screens have allowed identification of
specific genes, controlling a given trait with high accuracy.
Further studies will continue to unravel the unlimited potential of
RNAi to serve mankind.
26. “
”
Insight and discovery are functionally
separable. The one precedes the other.
Insight can happen everyday. Discovery
does not. Insight takes more intelligence,
but its discovery that is rewarded.
FRANCIS CRICK
THANK YOU
![WHAT IS RNA INTERFERENCE ?
INTERFERENCE means the act of interfering with something,
here, with RNA.
RNAi is an evolutionarily conserved mechanism triggered by dsRNA
molecules, to prevent the expression of specific genes or the
translation, causes sequence specific degradation of the targeted
mRNA molecules of that particular gene.
[ mRNA carry a genetic code identical to that of dsRNA]
It was also known as CO-SUPPRESSION, POST
TRANSCRIPTIONAL GENE SILENCING [ PTGS] in plants and
QUELLING in fungi.](data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7)