INTRODUCTION TO RNA AND TRANSCRIPTION
- Overview of RNA, its structure, and function in the process of transcription.
RNA STRUCTURE
- RNA is usually single-stranded.
- Contains ribose sugar and has uracil (U) instead of thymine (T) found in DNA.
- Primary Structure Example:
- Sequence: 5' AUGCGGCUACGUAACGAGCUUAGCGCGUAUACCGAAAGGGUAGAAC 3'
- Note on Ribose: Has a hydroxyl (OH) group at the 2'-carbon whereas DNA has hydrogen (H).
- Implication: RNA is more reactive than DNA.
- Secondary Structure: RNA can fold due to hydrogen bonding between complementary bases on the same strand, leading to complex structures.
TRANSCRIPTION OVERVIEW
- Definition: Transcription is the process of reading a DNA strand to create RNA.
- Central Dogma of Molecular Biology:
- DNA ⇌ RNA (Transcription) ⇌ Protein (Translation)
- Includes concepts of replication and reverse transcription.
TEMPLATE AND NON-TEMPLATE STRAND
- Template (coding) vs. Non-template (strand):
- RNA synthesis occurs complementary and antiparallel to the template strand.
- RNA polymerase reads the template strand in the 3' to 5' direction.
- mRNA is assembled from nucleotides in the 5' to 3' direction.
- Complementarity: Non-template is similar to mRNA, only differing by T in DNA replaced with U in RNA.
TRANSCRIPTION UNIT
- Definition: A transcription unit comprises a sequence of nucleotides in DNA that encodes a single RNA molecule.
- Structure: Typically includes:
- Promoter: where transcription begins
- RNA-coding region: sequence coding for RNA
- Terminator: sequence marking the end of transcription.
STAGES OF TRANSCRIPTION
- Transcription occurs in three stages:
- Initiation: Assembly of transcription apparatus at the promoter and beginning RNA synthesis.
- Elongation: Involves unwinding the DNA and adding nucleotides to the RNA strand.
- Termination: Recognition of the end of the transcription unit and separating RNA from DNA.
INITIATION
- Process includes:
- Promoter recognition by RNA polymerase.
- Formation of a transcription bubble.
- Creation of initial rNTP bonds and escaping the promoter.
CONSENSUS SEQUENCES
- Consensus Sequence: Most common nucleotides at specific DNA locations, e.g., TATA box 5'-TATAAA-3'.
- Used to identify promoter regions across genes.
- Consensus sequences in bacterial promoters:
- Common elements at positions -35 (TTGACA) and -10 (TATAAT).
RNA POLYMERASE IN BACTERIA
- Types of RNA polymerases in bacteria:
- Core enzyme: Set of five subunits involved in elongation.
- Sigma factor: Assists in locating promoters.
- Holoenzyme: Complete enzyme complex for transcription.
INITIATION IN BACTERIA
- Sigma factor associates with core enzyme to form a holoenzyme.
- Holoenzyme binds to promoter at -35 and -10 regions.
- Tightly binds, unwinding the DNA.
- Sigma factor released as RNA polymerase advances.
ELONGATION OF TRANSCRIPTION
- Characteristics during elongation:
- RNA polymerase creates a transcription bubble of about 18 nucleotides.
- Integrity of DNA is restored upstream (rewinds).
- If a mismatch occurs during transcription, the polymerase can backtrack and remove the faulty nucleotide.
TERMINATION OF TRANSCRIPTION IN BACTERIA
- Rho-Dependent Termination:
- Rho factor binds to RNA and approaches the RNA polymerase to help terminate transcription upon reaching a terminator sequence.
- Rho-Independent Termination:
- Involves inverted repeats followed by a string of adenines, causing RNA polymerase to pause leading to dissociation.
EUKARYOTIC TRANSCRIPTION OVERVIEW
- More complex than bacterial transcription, utilizing multiple RNA polymerases:
- RNA Polymerase I: Transcribes large rRNAs.
- RNA Polymerase II: Transcribes pre-mRNA and various small RNAs.
- RNA Polymerase III: Transcribes tRNA and small rRNAs.
- Complexity in eukaryotic promoters includes:
- Regulatory sequences such as TATA boxes, BRE, and others.
- Involvement of transcription factors for recognition and binding.
ELONGATION IN EUKARYOTES
- RNA polymerase maintains a transcription bubble and incorporates nucleotides matching the DNA template.
TERMINATION IN EUKARYOTES
- Varies by polymerase:
- Polymerase I requires termination factors similar to rho.
- Polymerase II uses protein Rat1 to help degrade RNA trailing after cleavage near 3' end.
- Polymerase III stops after encountering terminator sequences that include uracil strings.
SUMMARY OF TRANSCRIPTION
- RNA is generally single-stranded and plays various roles in transcription.
- Initiation is mediated by promoter sequences and other proteins.
- RNA polymerases synthesize RNA from the template strand and resemble the non-template strand, except for uracil and thymine differences.
- Diverse mechanisms exist for transcription termination.