Non-coding RNAs and Their Functions

Non-coding RNAs (ncRNAs) Overview

  • Definition: Non-coding RNAs (ncRNAs) are RNA molecules that do not translate into proteins but play critical roles in gene regulation and cellular functions.

  • Transcription Composition: In typical human cells, about 80% of transcription involves ncRNAs, while only 20% produces mRNAs. This indicates the vast functional potential of ncRNAs in cellular activities.

Key Roles & Functions of ncRNAs

  • Binding Abilities:

    • ncRNAs can bind to DNA/RNA through complementary base pairing, influencing DNA replication, transcription, and translation.

    • They also bind proteins or small molecules, forming structural scaffolds or binding sites.

  • Common Functions:

    1. Scaffold: Binds multiple components (e.g., proteins) to facilitate complex formation.

    2. Guide: Directs other molecules to specific cellular locations, such as guiding proteins to DNA.

    3. Alteration of Protein Function: Modifies how proteins interact, affecting activity and stability.

    4. Ribozyme: Functions as a catalyst, e.g., peptidyltransferase in ribosomes.

    5. Blocker: Physically inhibits cellular processes, such as blocking ribosome binding to mRNA.

    6. Decoy: Sequesters other ncRNAs to prevent their action.

Telomeres and Telomerase Functionality

  • Telomere Structure: The ends of linear eukaryotic chromosomes contain telomeres, which protect these ends from degradation.

  • Role of Telomerase: Telomerase, aided by TERC (telomerase RNA component), extends telomeres, crucial for replicating DNA at chromosome ends.

    • Process:

    1. Binding to chromosome ends.

    2. TERC acts as a guide/template.

    3. Adds excess DNA, allowing complete chromosome replication.

Effects of ncRNAs on Chromatin Structure & Gene Expression

  • HOTAIR: A key ncRNA regulating gene expression through scaffolding protein complexes that modify histones, thus silencing target genes. It binds to target genes to facilitate histone modifications.

RNA Interference (RNAi)

  • Mechanism: RNAi is mediated by microRNAs (miRNAs) or small-interfering RNAs (siRNAs) that bind to mRNA, inhibiting translation.

  • MicroRNAs: Endogenous, regulate gene expression.

    • Small-interfering RNAs: Exogenous, derived from viruses or experimental injections.

Non-coding RNAs in Protein Sorting

  • Signal Recognition Particle (SRP): Composed of ncRNA and proteins; it guides ribosomes to the endoplasmic reticulum (ER) during protein synthesis.

    • Function Steps:

    1. SRP binds to an ER signal sequence on the polypeptide.

    2. Translation pauses, SRP binds to an SRP receptor on the ER.

    3. GTP hydrolysis releases SRP, resuming translation and guiding the polypeptide into the ER.

CRISPR-Cas System for Genome Defense

  • CRISPR Type II System: Provides bacterial defense against bacteriophages.

  • Contains CRISPR genes (with unique spacers), tracrRNA, and Cas proteins.

    • Phases:

    1. Adaptation: Bacterial integration of foreign DNA into CRISPR.

    2. Expression: Transcription of the guiding RNAs.

    3. Interference: The guide RNAs lead Cas9 to cleave the foreign DNA.