19 Non Coding RNA

Introduction

  • The lecture begins with news of the passing of Jim Watson, a notable scientist known for co-discovering the structure of DNA along with Francis Crick.
  • Jim Watson's controversial remarks on intelligence and race are mentioned, highlighting the complexity of scientific figures.
  • Notable achievement: Jim Watson discovered the structure of DNA at age 25.
  • Personal anecdote shared: the speaker did not achieve similar milestones by age 25.

Key Concepts in Genetics

Definition of a Gene

  • Gene: A sequence of DNA that codes for a product (not exclusively a protein). This distinction is important for the upcoming discussions.

Inquiry About Human Genome

  • Questions are posed regarding the number of genes in the human genome, illustrating students' uncertainty on exact figures.
  • Common estimates for protein-coding genes range from 20,000 to 25,000.
  • Recognition of a gap in our understanding: uncertainty over how many genes are present and their functions, highlighting the complexity in genetic research.

Noncoding RNAs Overview

What are Noncoding RNAs?

  • Noncoding RNAs: These are RNA molecules that do not code for proteins but are products of genes.
  • They are classified by length:
    • Long noncoding RNAs (longer than 200 nucleotides).
    • Short noncoding RNAs (e.g., microRNAs).

Abundance

  • Noncoding RNAs are more abundant than messenger RNAs (mRNAs) in cells.
    • TRNAs (transfer RNAs) and ribosomal RNAs are examples of abundant noncoding RNAs.

Function of Noncoding RNAs

  • Noncoding RNAs can participate in various molecular interactions, including:
    • Binding to DNA and influencing transcription.
    • Interacting with mRNAs to regulate stability and translation.
    • Binding to proteins to influence their functional properties (e.g., through allosteric effects).
    • Functioning as scaffolds to bring other molecules together.

Mechanisms of Noncoding RNA Action

Regulatory Roles

  • Noncoding RNAs play a critical role in gene expression regulation, such as:
    • Serving as guides to specific RNA or DNA sequences.
    • Binding to proteins and modifying their structure and function.
    • Acting as blockers or decoys to inhibit the function of other molecules, like microRNAs.

Examples of Mechanisms

  • MicroRNAs: Short RNA molecules that can inhibit translation by binding to mRNAs.
  • Decoy Noncoding RNAs: These can bind to microRNAs, preventing them from inhibiting target mRNAs.

RNA Interference

Mechanism of RNA Interference

  • RNA interference (RNAi) is a process through which noncoding RNAs regulate gene expression by binding to mRNAs, leading to either destabilization or inhibition of translation.
  • MicroRNAs: Normal part of the cell's regulatory mechanism; encoded by genes, they repress mRNA translation or lead to degradation.
  • Small Interfering RNAs (siRNAs): Exogenous and can be introduced into cells to knock down expression of targeted genes.

Process of MicroRNA Functioning

  1. Transcription: Primary microRNA is transcribed and processed into pre-microRNA.
  2. Processing: Dicer enzyme cuts the pre-microRNA into smaller double-stranded RNA fragments.
  3. RISC Complex Formation: One strand of the double-stranded RNA is incorporated into the RISC complex and targets complementary mRNAs for regulation.
  4. Regulatory Outcomes: Depending on complementarity, target mRNA can be degraded or its translation inhibited.

CRISPR-Cas System

Overview

  • CRISPR technology originated from the study of bacterial gene sequences that include repetitive regions that provide immunity against viruses.
  • This system has been harnessed as a powerful tool for gene editing in many organisms, including humans, by introducing targeted changes to DNA sequences.

Mechanism of CRISPR Technology

  1. Adaptation: Bacteria acquire new sequences from viruses and integrate them into their CRISPR locus, creating a DNA memory of past infections.
  2. Expression: The CRISPR sequences are transcribed into RNA, which guides Cas9 proteins to the corresponding viral DNA for interference.
  3. Interference: Cas9 acts as an endonuclease that cuts the viral DNA, preventing infection from occurring in the future.

Practical Applications

  • Gene editing: Researchers can design guide RNAs based on human genes to target specific sequences for mutation, analysis, or correction, potentially treating genetic disorders.

Ethical Considerations

  • The discussion hints at concerns over the implications of gene editing, especially concerning human embryos and the modification of the human genome.
  • The potential for CRISPR technology to be misused or to result in unintended consequences raises ethical questions around its application in humans.

Conclusion

  • The lecture concludes with a reflection on the exciting developments in the field of genetics, particularly with regard to noncoding RNAs and CRISPR technology, and the ongoing exploration of how these molecules affect cell biology and the potential for genetic manipulation.