1. Non-coding RNAs play important roles in various biological processes and diseases. They are not translated into proteins but instead regulate gene expression.
2. Mutations or imbalances in non-coding RNAs can lead to diseases such as cancer, Prader-Willi syndrome, autism, cartilage-hair hypoplasia, Alzheimer's disease, and autoimmune diseases.
3. Prader-Willi syndrome is caused by the deletion of snoRNA gene clusters and is characterized by over-eating and learning difficulties. Autism has been linked to duplications of the SNORD115 gene cluster and changes in the expression of circular RNAs and microRNAs.
Almost 98 of the human genome does not encode proteins
o The non coding transcripts less than 200 bases are called small non
coding RNA and comprise of tRNA, rRNA, miRNA, snoRNA, piwi
interacting RNA (pi RNA)
o RNA molecules that are of more than 200 bases in length are known
as long non coding RNA (
o lncRNAs are more than 200 nucleotides in length and also can be
more than 2 Kb
o Such long noncoding RNAs usually have limited coding potential due
to the absence of open reading frames, 3 UTR and termination
region while their coding potential is less than 100 amino acids
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
Almost 98 of the human genome does not encode proteins
o The non coding transcripts less than 200 bases are called small non
coding RNA and comprise of tRNA, rRNA, miRNA, snoRNA, piwi
interacting RNA (pi RNA)
o RNA molecules that are of more than 200 bases in length are known
as long non coding RNA (
o lncRNAs are more than 200 nucleotides in length and also can be
more than 2 Kb
o Such long noncoding RNAs usually have limited coding potential due
to the absence of open reading frames, 3 UTR and termination
region while their coding potential is less than 100 amino acids
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
Transcriptomics is the study of RNA, single-stranded nucleic acid, which was not separated from the DNA world until the central dogma was formulated by Francis Crick in 1958, i.e., the idea that genetic information is transcribed from DNA to RNA and then translated from RNA into protein.
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.
SNP (Single Nucleotide Polymorphic), SNP mapping, SNP profile, SNP types, SNP analysis by gel electropherosis and by mass spectrometry, SNP effects, single strand conformation polymorphism, SNP advantages and disadvantages and application of SNP profile in drug choice
Alternative splicing is a deviation from the conventional splicing as it removes introns in a different manner. It has a lot of significance in the development of diseases like cancers and in plants adapting to various stress conditions.
I have described in this presentation the critical points in the maturation of small non-coding RNA especially miRNA and its role in the development and diagnosis of specific psychiatric disorders
Transcriptomics is the study of RNA, single-stranded nucleic acid, which was not separated from the DNA world until the central dogma was formulated by Francis Crick in 1958, i.e., the idea that genetic information is transcribed from DNA to RNA and then translated from RNA into protein.
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.
SNP (Single Nucleotide Polymorphic), SNP mapping, SNP profile, SNP types, SNP analysis by gel electropherosis and by mass spectrometry, SNP effects, single strand conformation polymorphism, SNP advantages and disadvantages and application of SNP profile in drug choice
Alternative splicing is a deviation from the conventional splicing as it removes introns in a different manner. It has a lot of significance in the development of diseases like cancers and in plants adapting to various stress conditions.
I have described in this presentation the critical points in the maturation of small non-coding RNA especially miRNA and its role in the development and diagnosis of specific psychiatric disorders
mRNA stability and localization.RNA is critical at many stages of gene expression. How frequently it will be translated, how long it is likely to survive, and where in the cell it will be translated. RNA cis-elements & associated proteins
Sequencing genes and genomes in biology. The most important technique available to the molecular biologist is DNA sequencing, by which the precise order of nucleotides in a piece of DNA can be determined
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The Roman Empire, a vast and enduring power, stands as one of history's most remarkable civilizations, leaving an indelible imprint on the world. It emerged from the Roman Republic, transitioning into an imperial powerhouse under the leadership of Augustus Caesar in 27 BCE. This transformation marked the beginning of an era defined by unprecedented territorial expansion, architectural marvels, and profound cultural influence.
The empire's roots lie in the city of Rome, founded, according to legend, by Romulus in 753 BCE. Over centuries, Rome evolved from a small settlement to a formidable republic, characterized by a complex political system with elected officials and checks on power. However, internal strife, class conflicts, and military ambitions paved the way for the end of the Republic. Julius Caesar’s dictatorship and subsequent assassination in 44 BCE created a power vacuum, leading to a civil war. Octavian, later Augustus, emerged victorious, heralding the Roman Empire’s birth.
Under Augustus, the empire experienced the Pax Romana, a 200-year period of relative peace and stability. Augustus reformed the military, established efficient administrative systems, and initiated grand construction projects. The empire's borders expanded, encompassing territories from Britain to Egypt and from Spain to the Euphrates. Roman legions, renowned for their discipline and engineering prowess, secured and maintained these vast territories, building roads, fortifications, and cities that facilitated control and integration.
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Culturally, the Romans were eclectic, absorbing and adapting elements from the civilizations they encountered, particularly the Greeks. Roman art, literature, and philosophy reflected this synthesis, creating a rich cultural tapestry. Latin, the Roman language, became the lingua franca of the Western world, influencing numerous modern languages.
Roman architecture and engineering achievements were monumental. They perfected the arch, vault, and dome, constructing enduring structures like the Colosseum, Pantheon, and aqueducts. These engineering marvels not only showcased Roman ingenuity but also served practical purposes, from public entertainment to water supply.
2. Non-coding RNA
• Not translated into a protein
• tRNAs, rRNAs, microRNAs, siRNAs, piRNAs, snoRNAs,
snRNAs, exRNAs, scaRNAs and Xist and HOTAIR.
• NGS : New information about genomic organization & gene
expression regulation
History and discovery
• Friedrich Miescher
• Francis Crick
• Alanine tRNA
2
6. Biological roles
• ncRNAs
1. In translation: Ribonucleoprotein
2. In RNA splicing: splicing reaction, self-splicing, snoRNA HBII-52
3. In DNA replication: Y RNAs, lupus erythematosus
4. In gene regulation: expression of genes, This regulation can occur in
trans or in cis
5. In genome defense: piRNAs
6. Chromosome structure: Telomerase
7. As a hormone: ecdysone hormone, development of several endocrine
organs
6
7. Roles in disease
As with proteins, mutations or imbalances in the ncRNA repertoire
within the body can cause a variety of diseases.
1. Cancer
2. Prader–Willi syndrome
3. Autism
4. Cartilage–hair hypoplasia
5. Alzheimer's disease
6. Autoimmune Diseases
7. Osteoporosis
7
8. 1. Cancer
• Abnormal expression patterns
• Chronic lymphocytic leukemia miR-16-1 and miR-15 primary
• Non-small cell lung carcinoma rare SNP : mir-196a2
• Breast cancer miR-17 and miR-30c
• Most important agent in preventing tumor p53
8
9. • Multifunctional regulators in all biological processes
• ENCODE & FANTOM
• Bioinformatic predictions suggest that human miRNAs regulate
over 60% of transcripts.
• Long noncoding RNAs
• Lack functional open reading frames
• Heterogeneous mechanisms
• NATs
9
10. • MiRNAs: proliferation, resistance to apoptosis, angiogenesis,
invasion and metastasis
• CLL : miR‐15 and miR‐16 13q13.4
• More than 50% of human tumours: LOF p53
• HCC: MiR‐26a
• Colon cancer: LIN28B
• Long noncoding RNAs: malignant
• MALAT1 NSCLC
• HOTAIR colorectal, liver, pancreatic, breast and gastric
cancers
10
11. • Sage
• Microarray
• RNA-seq
• Cage
• RT-qPCR
• ISH
• FISH
• Northern blot analysis
11
12. 2. Prader–Willi syndrome
• Deletion of the 29 copies of the C/D box snoRNA
• Developmental disorder: over-eating & learning difficulties
• Weak muscles, poor feeding & slow development
• PWS is not generally inherited
• Prader–Willi syndrome has no cure
12
13. The PW genes are the SNRPN and NDN necdin genes, along with clusters
of snoRNAs:
1. SNORD64, SNORD107, SNORD108
2. two copies of SNORD109
3. 29 copies of SNORD116
4. 48 copies of SNORD115
13
17. 3. Autism(ASD)
• Developmental disorder
• rubella, alcohol, cocaine, pesticides, and air pollution
• No treatment has been proven to cure ASD
• SNORD115 gene cluster duplicated
17
20. • Inheritability of 45–56%
• WES CNVs
• CNVs may also lead to the generation of chimeric genes
• Chimeric genes
• Microdeletion
• Recent studies have shown that epigenetic factors, including DNA
methylation, hystone modifications and microRNAs (miRNAs), could play
an important role in predisposition to autism.
• Down-regulation of miR-6126
• Circular RNAs (circRNAs) NLGN1, STAG1, HSD11B1, VIP, and UBA6
20
21. 4. Cartilage–hair hypoplasia(CHH)
• Mutations within RNase MRP A-to-G transition at nucleotide 70
• short stature, sparse hair, skeletal abnormalities and a suppressed
immune system, Lymphopenia
• PI3K-Akt signaling
• G2 phase to mitosis
21
28. 6. Autoimmune Diseases
• Ads are a family of disorders characterized by the body’s immune
response being directed against its own tissues, with consequent
chronic inflammation and tissue damage
• HOX transcript antisense RNA (HOTAIR)
• Overexpression of lncRNAs in T cells and B cells
• GAPLINC
• The circRNAs can interfere with miRNA functions
• circRNAs may be diagnostic RA markers or potential therapeutic
targets
28
33. 7. Osteoporosis
• Osteoporosis is a common metabolic bone disease, influenced by
genetic and environmental factors
• miR-33-5p: osteoblastogenesis
• miRNA-194: osteoblast differentiation
• miR-96
33
34. 1. Noncoding RNAs in disease PMCID: PMC6174949
2. Non-coding RNAs in cancer: platforms and strategies for investigating the genomic “dark matter”
3. Noncoding RNAs in Alzheimer's disease.
4. Alzheimer Disease Pathogenesis: Insights From Molecular and Cellular Biology Studies of Oligomeric Aβ and Tau Species
5. Are Circulating MicroRNAs Peripheral Biomarkers for Alzheimer’s Disease?
6. Prader-Willi syndrome: reflections on seminal studies and future therapies.
7. Epigenetic therapy of Prader-Willi syndrome.
8. Prader-Willi-Like Phenotype Caused by an Atypical 15q11.2 Microdeletion
9. Targeting the histone methyltransferase G9a activates imprinted genes and improves survival of a mouse model of Prader-Willi syndrome
10. Deficiency in prohormone convertase PC1 impairs prohormone processing in Prader-Willi syndrome
11. Targeted CRISPR disruption reveals a role for RNase MRP RNA in human preribosomal RNA processing
12. The human long non-coding RNA gene RMRP has pleiotropic effects and regulates cell-cycle progression at G2
13. Prediction and prioritization of autism-associated long non-coding RNAs using gene expression and sequence features
14. A heritable profile of six miRNAs in autistic patients and mouse models
15. An Overview of the Main Genetic, Epigenetic and Environmental Factors Involved in Autism Spectrum Disorder Focusing on Synaptic Activity
16. Genome-wide, integrative analysis of circular RNA dysregulation and the corresponding circular RNA-microRNA-mRNA regulatory axes in autism
17. Long Noncoding RNAs and Circular RNAs in Autoimmune Diseases
18. A micropeptide encoded by lncRNA MIR155HG suppresses autoimmune inflammation via modulating antigen presentation
19. Circular RNAs in immune responses and immune diseases
20. The roles of miRNA, lncRNA and circRNA in the development of osteoporosis
34