Fascinating world of Noncoding RNAs Fascinating world of

Fascinating world of Non-coding RNAs

Fascinating world of Non-coding RNAs Non-coding RNA (nc. RNA) is a RNA molecule that functions w/o being translated into a protein

How big is nc. RNA’s world

Fascinating world of Non-coding RNAs • t. RNA & r. RNA • 4. 5 S & 7 S RNA (Signal Recognition Particles) • sn. RNA – Pre-m. RNA splicing • sno. RNA – r. RNA modification • si. RNA – small interfering RNA • g. RNA – guide RNA in RNA editing • Telomerase RNA – primer for telomeric DNA synthesis • tm. RNA is a hybrid molecule, half t. RNA, half m. RNA • Xist: The X chromosome silencing is mediated by Xist – a 16, 000 nt long nc. RNA • sh. RNA (small heterochromatic RNAs ): expresses only one allele while other is silenced • LNA Locked Nucleic Acid • pi. RNA Piwi-interacting RNA

Regulatory nc. RNAs • Transcriptional regulators • Translational regulators • anti-sense mechanism • RNA interference • Modulators of protein function (altering their structure, enzymatic activities) • Regulators of RNA and protein distribution

House keeping nc. RNAs 4. 5 S & 7 S RNA

4. 5 S RNA (E. coli) and 7 S RNA (human) signal recognition particle (SRP)(RNP) Signal sequence SRP ribosome m. RNA SRP receptor translocon SRP Endoplasmatic reticlum membrane • SRP recognizes signalling amino acid sequence in the N-terminus of growing polypeptide chain • Upon signal recognition, ribosome is attached to endoplasmatic reticlum so that the protein, made by ribosome, enters the secretory pathway

Structure of SRP RNA holds together the protein subunits of SRP as well as helps to bind to ribosome

sn. RNP (spliceosome)

Small nucleolar RNA (sno. RNA) Class of small RNA molecules that primarily guide chemical modifications of other RNAs, mainly ribosomal RNAs, transfer RNAs and small nuclear RNAs.

Small nucleolar RNA (sno. RNA) There are two main classes of sno. RNA, 1. C/D box which are associated with methylation, and 2. H/ACA box which are associated with pseudouridylation.

si. RNA short interfering RNA or silencing RNA, is a class of double-stranded RNA molecules, 20 -25 nucleotides in length, that play in the RNA interference si. RNA interference Disrupts Hepatitis B Virus

Classes of si. RNAs 1. Trans-acting short interfering RNAs (tasi. RNA): 2. Repeat-associated short interfering RNAs (rasi-RNAs): 3. Scan RNA (scn RNA): 4. Long si. RNAs (lsi. RNAs):

Repeat associated small interfering RNA (rasi. RNA) These are involved in: • establishing and maintaining heterochromatin structure, • controlling transcripts that emerge from repeat sequences, and • silencing transposons and retrotransposons

Trans-acting short interfering RNAs (tasi. RNA) They convert RNA viral transcripts to ds. RNA by the action of RNA dependent RNA polymerase (Rd. RP) and prevent their transcription (post- transcriptional gene silencing )

Scan RNA (scn RNA): They are involved in scanning DNA sequences in order to induce genome rearrangement. scn RNAs from the micro-nucleus (in cilliates like Paramecium) are derived and they eliminate corresponding loci from its own genome while giving rise to macronucleus.

Long si. RNAs (lsi. RNAs): These are about 30 -40 nucleotides in length. Their formation is induced in response to bacterial infection or growth conditions. One of the lsi. RNAs targets a protein that gives resistance against bacterial infection(PTGS).

Guide RNA (g. RNA): the editor of RNA

Guide RNA The Editosome Complex

Guide RNA C to U & A to I Insertion & deletion

tm. RNA and trans-translation • tm. RNA is a hybrid molecule, half t. RNA, half m. RNA • tm. RNA helps to rescue ribosomes, bound to m. RNA which lacks the termination codon • In addition, tm. RNA adds a degradation signal to nascent protein

tm. RNA Ala The tagged protein is degraded due to the signal sequence in C-terminus

Xist RNA & Silencing of one female X chromosome in mammals • The X chromosome silencing is mediated by Xist – a 16, 000 nt long nc. RNA • Xist recruit a specific histone isoform – H 2 A 1. 2 which maintains the chromosome in inactive state • Additionally, Xist containing complexes recruit histone deacetylases and methylases

Xist RNA & Silencing of one female X chromosome in mammals

Piwi interacting RNA (pi. RNA) pi. RNAs (26 -31 nt) (interact with piwi protein) are thought to be involved in gene silencing of transposons (during spermatogenesis to maintain fertility. PIWI = P-element induced wimpy (weak and ineffectual) testis in Drosophila

LNA: Locked Nucleic Acid Third-generation antisense nucleotides are Single-stranded LNA oligonucleotides & si. RNA LNA have high binding capacity

mi. RNAs are post-transcriptional regulators that bind to complementary sequences on target messenger RNA transcripts (mi. RNAs), usually resulting in translational repression or target degradation and gene silencing

sh. RNAs and Genetic imprinting • Genetic imprinting = expression of only one allele of gene. • The differences of expression from both alleles Activity of small heterochromatic RNAs (sh. RNAs) appear to be essential for establishing and maintaining the imprinted status of genes

sh. RNAs and Genetic imprinting recognition of DNA or nascent RNA transcripts by a RISC-like targeting complex. RNA-mediated clustering of heterochromatic domains

sh. RNA