Central dogma: from genome to proteins I: Transcription

Haixu Tang

School of Informatics

The flow of genetic information

Transcription: DNA RNA

• Copy a particular portion of its DNA nucleotide sequence a gene into an RNA nucleotide sequence.

• The information in RNA, although copied into another chemical form, is still written in essentially the same language as it is in DNA the language of a nucleotide sequence.

Genes can be expressed with different efficiencies

The structure of RNA

RNA (single strand) can fold into specific structure

DNA transcription produces a single-stranded RNA

molecule, complementary to one strand of DNA

RNA polymerase uses DNA as template

DNA polymerase vs. RNA polymerase

• RNA polymerase is more error prone: 10-4 vs 10-7

• A modest proofreading mechanism

• RNA stores information only temporarily

Principal Types of RNAs Produced in Cells

mRNAs messenger RNAs, code for proteins

rRNAs ribosomal RNAs, form the basic structure of the ribosome and catalyze protein synthesis

tRNAs transfer RNAs, central to protein synthesis as adaptors between mRNA and amino acids

snRNAs small nuclear RNAs, function in a variety of nuclear processes, including the splicing of pre-mRNA

snoRNAs small nucleolar RNAs, used to process and chemically modify rRNAs

Other noncoding RNAs function in diverse cellular processes, including telomere synthesis, X-chromosome inactivation, and the transport of proteins into the ER

The transcription cycle

Initiating signal

Directions of transcription

Types of RNA polymerases in eukaryotic cells

TYPE OF POLYMERASE GENES TRANSCRIBED

RNA polymerase I 5.8S, 18S, and 28S rRNA genes

RNA polymerase II all protein-coding genes, plus snoRNA genes and some snRNA genes

RNA polymerase III tRNA genes, 5S rRNA genes, some snRNA genes and genes for other small RNAs

Several important differences between the bacterial and eucaryotic RNA polymerases.

• .While bacterial RNA polymerase (with factor as one of its subunits) is able to initiate transcription on a DNA template in vitro without the help of additional proteins, eucaryotic RNA polymerases cannot. They require the help of a large set of proteins called general transcription factors, which must assemble at the promoter with the polymerase before the polymerase can begin transcription.

• Eucaryotic transcription initiation must deal with the packing of DNA into nucleosomes and higher order forms of chromatin structure, features absent from bacterial chromosomes.

Initiation of transcription of

a eucaryotic gene by RNA polymerase II

Consensus sequences found in the vicinity of

eucaryotic RNA polymerase II start points

3D structure of TBP (TATA-binding protein) bound to DNA

Transcription initiation

Supercoiling of DNA

Transcription in Eukaryotic cells

RNA processing: pre-RNA mature RNA

• 5’ Cap

• Poly-A

• Splicing

• Editing

• Coupled with elongation

5’ Cap of RNA

Splicing

Splicing reactions and Lariats

Splicing signals

Alternative splicing

The RNA splicing

mechanism

Variation in intron and exon lengths

Splicing errors

Additional factors for correct splicing site recognition

• RNA factory concept

• Exon definition hypothesis

The "RNA factory" concept

The exon definition hypothesis

Three major type of splicing mechanism

Abnormal splicing cause

disease

Self splicing

PolyA addition

Exportation of mature RNA