1. REGULATION OF SMALL RNA
Alicia Gómez González
Advanced Genetics Master’s degree

2. INDEX Introduction Small RNAs miRNAs siRNAs piRNAs Others Conclusions
Bibliography
(Sciencephoto library)

3. Chromatin associated ncRNA
1. INTRODUCTION
tRNA – Transfer RNA
rRNA – ribosomal RNA
Long ncRNA (> nt)
Short ncRNA ( nt)
(The molecular ecogolist)
Chromatin associated ncRNA
2- 3 % Proteins - mRNA
The rest – non coding RNA (ncRNA)
snRNA
snoRNA
sRNAs

4. 2. SMALL RNAs sRNA miRNA – micro RNA Function
Post-transcription: Supress translation of different mRNA nt
- Translation inhibition
- Translation activation
siRNA – Small interfering RNA nt
Pre-transcription: affects chromatine structure
sRNA nt
Argonaute proteins
piRNA – Piwi-associated RNA nt
They are originated by longer fragments of RNA
RISC
(Parker & Barford, 2006)

5. 3. miRNA - microARN 21-23 nt long > 850 miRNA in humans
Tissue specific miRNA
Precursors → genome encoded
30-40% of mRNA is regulated by miRNA post- transcriptional silencing
A single miRNA molecule can regulate >100 genes
Alterations
Diseases like cancer
(Großhans & Filipowicz, 2008)

6. 3. miRNA – Biogenesis & Action
Nucleus
1. RNA pol – pri-miRNA transcription
2. Drosha – cleavage to pre-miRNA
Cytoplasm
3. Dicer – cleavage to miRNA duplex
4. RISC COMPLEX – mature miRNA
ACTION
1. Translational repression mistmatches
2. mRNA degradation complete complementarity
(Yi, Piazza, Su, & Xi, 2013)

7. 4. siRNA - small interfering RNAs
21-23 nt long
(Großhans & Filipowicz, 2008)
Precursors → double strand RNAs → they can be synthetically designed
Defense agains viral infection
Different roles
Supress TE in somatic cells
Regulate protein coding genes

8. 4. siRNA – Pathway ORIGIN Endogenous Exogenous (viral ) BIOGENESIS
dSRNA
dsRNA
shRNA
BIOGENESIS
Nucleus
1. RNA pol – dsRNAs
2. Dicer – cleavage to siRNA
Cytoplasm
3. RISC COMPLEX – mRNA silencing
(Großhans & Filipowicz, 2008)

9. 5. piRNA – PIWI interacting RNAs
Independent of Drosha /Dicer
26-30 nt long
Piwi
Ago3
Aubergine
Association with PIWI proteins → germline specific argonaute proteins
Protection against TE in the germ line
Precursors → single stranded transcripts
D.melanogaster
ORIGIN
piRNA clusters
Individual transposons
Some protein coding genes
(Wilhelm & Pascal, 2016)

10. 5.piRNA -biogenesis PRIMARY – zuc mediated SECONDARY- Ping-pong cycle
Somatic follicule cells
Germline cells
PRIMARY – zuc mediated
SECONDARY- Ping-pong cycle
Maternal source
Antisense transcript
piwi
Zuc endonuclease 5’ 3’
sense transcript
Antisense transcript 5’ 3’
Aub 5’
Aub
piwi 5’ 3’ 3’
PING-PONG 5’ 3’
Ago3 5’ 3’
Ago3 5’ 3’
Inmune system vs TE

11. 5. piRNA - functions Regulation of Transposable Elements
Transcriptional silencing
Epigenetics
(Wilhelm & Pascal, 2016)
(Susanne & Gunter, 2011)

12. Many types → still a lot of research
7. CONCLUSIONS
Precursors
Main function
Enzymes
Drosha , Dicer , Ago
miRNA
DsHairpin transcriptis
mRNA repressing/degradation
Dicer , Ago
siRNA
Ds transcripts
TE and viral infections inactivation
Ss transcripts
Regulation of TE in germ cells
PIWI complex
piRNA
Many types → still a lot of research
Alterations in this molecules are related with infections, ilnesses… → interesting for therapeutic purposes
Ex : OncomiRNAs
Mirtron

13. 8. BIBLIOGRAPHY
Goodchild, J. (Ed. . (2011). Therapeutic Oligonucleotides. Methods and Protocols. Humana Press.
Großhans, H., & Filipowicz, W. (2008). Q & A The expanding world of small RNAs. Nature, 451(January).
Huang, X., Fejes Tóth, K., & Aravin, A. A. (2017). piRNA Biogenesis in Drosophila melanogaster. Trends in Genetics, 33(11), 882–894.
Parker, J. S., & Barford, D. (2006). Argonaute: a scaffold for the function of short regulatory RNAs. Trends in Biochemical Sciences, 31(11), 622–630.
Sciencephoto library , acessed [01/12/2018] , available at :https: // /media/526016/view
Susanne, R., & Gunter, M. (2011). Small RNAs derived from longer non-coding RNAs. Biochimie, 93, 1905–1915.
The molecular ecologist; available at: debiasse/. Acessed [02/12/2018]
Wilhelm, D., & Pascal, B. (Eds.). (2016). Advances in Experimental Medicine and Biology 886, Non-coding RNA and the Reproductive System. Springer.
Yi, B., Piazza, G. A., Su, X., & Xi, Y. (2013). Micro RNA and cancer chemoprevention. Cancer Prevention Research, 6(5), 401–409.