Chapter 11 – The Expression of Genetic Information via Genes II: Non-coding RNAs

Chapter 11 – The Expression of Genetic Information via Genes II: Non-coding RNAs

Overview of Non-coding RNAs

• Non-coding RNAs (ncRNAs) are RNA molecules that do not encode polypeptides.

• The human genome contains approximately 22,000 protein-coding genes, but in most cell types, ncRNAs are more abundant than mRNAs, comprising about 80% of transcription.

• Historically, there has been a bias towards DNA and protein in biological education, which this chapter aims to address by focusing on ncRNA structures and functions.

• ncRNAs can affect the ability of mRNAs to be translated or degraded

Properties and Functions of ncRNAs:

• Binding Ability:

  • ncRNAs can bind to various macromolecules through complementary base pairing, affecting processes such as transcription, translation, and DNA replication.

  • They can bind to DNA, other RNAs, proteins, or small molecules.

• Common Functions:

  • Scaffold: Binds multiple proteins to form complexes.

  • Guide: Directs molecules to specific cellular locations.

  • Alteration of Protein Function: Affects protein stability and functionality by binding.

  • Ribozyme: Acts as a catalyst (e.g., peptidyl transfer in ribosomes).

  • Blocker: Prevents cellular processes (e.g., blocking ribosome binding). (binds a molecule that is not an ncRNA)

  • Decoy: Binds other ncRNAs, preventing their function. (binds to an ncRNA)

• Examples of ncRNAs:

  • Telomerase RNA component (TERC): critical for DNA replication.

  • Xist RNA: involved in chromosome compaction and inactivation in females.

  • HOTAIR: modulates chromatin structure and gene transcription.

  • Transfer RNA (tRNA) and Ribosomal RNA (rRNA): involved in translation.

  • microRNA (miRNA) and small-interfering RNA (siRNA): regulate mRNA expression.

  • CRISPR RNA (crRNA): genome defense, guides an endonulease to foreign DNA, like the DNA of a bacteriophage

Role of ncRNAs in Eukaryotic DNA Replication

• Telomeres are repetitive sequences at the ends of chromosomes that protect them from degradation.

  • In humans, the sequence is 5ʹ–GGGTTA–3ʹ.

• Telomerase, containing TERC, extends telomeres to prevent shortening during DNA replication.

• Telomere lengthening occurs in three steps:

  1. Binding: TERC complements the DNA repeat and guides telomerase.

  2. Polymerization: TERC serves as a template for synthesizing DNA repeat sequences.

  3. Translocation: Telomerase moves to the new DNA end for further nucleotide addition.

Effects of ncRNAs on Chromatin Structure and Transcription

• HOTAIR is an ncRNA that regulates gene expression by binding protein complexes that modify histones (proteins that help organize and package DNA in the cell nucleus into a structure called chromatin, allowing for proper gene regulation and DNA protection), leading to gene silencing.

Effects of ncRNAs on Translation and mRNA Degradation

• RNA Interference (RNAi):

  • Revealed that double-stranded RNA is more effective at silencing mRNA than antisense RNA.

  • Conducted using the mex-3 gene in C. elegans, showcasing the impact of double-stranded RNA on mRNA levels.

• MicroRNAs (miRNAs) and Small-interfering RNAs (siRNAs) are essential in RNAi:

  • miRNAs originate from eukaryotic genes and regulate about 60% of protein-coding genes.

  • siRNAs usually arise from exogenous sources and are technically relevant for research.

• RNA processing involves:

  1. Synthesis of primary-miRNA in the nucleus, which forms a hairpin structure.

  2. Processing by Dicer to create double-stranded miRNA or siRNA.

  3. Incorporation into the RNA-induced silencing complex (RISC) where one strand is degraded, and the other guides the silencing of target mRNAs.

Non-coding RNAs and Protein Sorting

• The Signal Recognition Particle (SRP) directs proteins to their functional locations:

  • Comprises 1 ncRNA and multiple proteins in eukaryotes.

  • SRP RNA: serves as a scaffold for protein binding and stimulates GTP hydrolysis during protein targeting to the ER.

Non-coding RNAs and Genome Defense

• The CRISPR-Cas system protects bacteria from bacteriophages:

  • Involves a CRISPR gene, tracrRNA, and various Cas proteins.

• Main phases of CRISPR-Cas defense:

  1. Adaptation: Inserting foreign DNA into the CRISPR locus.

  2. Expression: Transcribing CRISPR into crRNA and forming the tracrRNA-crRNA complex.

  3. Interference: Complex binds and cleaves bacteriophage DNA.

• the tracrRNA is an ncRNA with a region that is complimentary to the repeat of the pre-

• RNA polymerase binds to the promoter and transcription rate (decrease or increases????

Role of ncRNAs in Human Disease and Plant Health

• Abnormal ncRNA levels linked to cancers, with examples like HOTAIR acting as an oncogene.

• ncRNAs also play critical roles in plant health, impacting growth and stress responses, making them significant for agriculture.

Note: Include specific ribozyme functions and additional ncRNA examples discussed in full text when applicable for in-depth understanding.