Dr. Aga Syed SameerCSIR LecturerDepartment of Biochemistry,Medical College,Sher-I-Kashmir Institute of Medical Sciences, Bemina, Srinagar, Kashmir, 190018. India.

NUCLEIC ACIDS

ChemistryRNA: Structure & Functions

• RNA (RiboNucleic Acid), like DNA, is a form of nucleic acid found in cells. RNA, like DNA, is a polymer composed of nucleoside monophosphates

• The bases in RNA are adenine (A), guanine (G), cytosine (C), and uracil (U)

• These are the same bases as DNA except that the base uracil is used in place of thymine (T)

• Unlike DNA, RNA is rarely composed of two strands base paired with each other.

• Instead, RNA exists as a single-stranded entity, though extensive regions of many RNAs may form double helices within themselves by the base pairing rules

RNA

The three predominant forms of RNA are all involved in translating the genetic information in the sequence of bases in DNA to a sequence of amino acids in proteins.

They are called:

messenger RNA (mRNA),

transfer RNA (tRNA), and

ribosomal RNA (rRNA)

Types of RNA

• mRNA is made directly from DNA, so mRNAcarries the genetic information in the DNA sequence from the cell nucleus to the ribosomes where proteins are made

• Thus, mRNA serves as the mediator in converting the information in DNA into the sequence of amino acids in proteins

• Information is organized in DNA (and mRNA) in a sequence of three nucleotides called as codons

• One codon specifies the incorporation of specific amino acid in protein

mRNA

• tRNAs serve as adaptor molecules for the translation the genetic code

• One end of the tRNA contains a three nucleotide sequence called the anticodon loop that is complementary to the codon of the mRNA

• The other end of the tRNA is covalently attached to a specific amino acid

• Because the amino acid carried by a tRNA is specific for each anticodon and each anticodon is complementary to the codons in mRNA, thus tRNA provides the link between nucleic acid sequence and amino acid sequence for a protein during translation

tRNA

• tRNAs are made up of 74- 95 nucleotides about 20% of which are modified bases found exclusively in its sequence.

• 50 different types of modified bases have been observed in several hundred characterized to date.

• All tRNAs have a common secondary structure formed due to complementary base pairing in the primary sequence of tRNA.

tRNA

• tRNAs contain numerous chemical modifications to the bases within them.

• Pseudouridine,

• Ribothymidine,

• Dihydrouridine,

• Inosine

• Methyl cytidine

• Methyl guanosine

tRNA

• The secondary structure of tRNA is called the cloverleaf structure as shown.

• It has a 5' -phosphate formed by RNase P cleavage and a 7 bp stem formed by base pairing between 5’- and 3'-ends of the tRNA

tRNA - Clover Leaf Model

• The invariant residues 74-76 (i.e. the 5'-CCA-3') which are added during processing in eukaryotes are not included in this base pairing region

• This stem is called the amino acceptor stem as it is site for the amino acid binding during the process of translation

tRNA - Clover Leaf Model

• The next secondary structure is D-arm which is composed of a 3 or 4 bpstem and a loop called the D-loop (DHU-loop) usually containing the modified base dihydrouracil.

• The next structural feature consists of a 5 bp stem and a seven residue loop in which there are three adjacent nucleotides called the anticodon which are complementary to the codon sequence (a triplet in the mRNA)that the tRNArecognizes

tRNA - Clover Leaf Model

• The presence of inosine in the anticodon gives a tRNA the ability to base-pair to more than one codon sequence

• Next there is a variable arm which can have between three and 21 residues and may form a stem of up to 7 bp.

• The final major feature of secondary structure is the T -arm or TψC -arm which is composed of a 5 bp stem ending in a loop containing the invariant GTψC.

tRNA - Clover Leaf Model

• The tertiary structure of the tRNA looks like the letter L, with the anticodon at one end & the amino acid acceptor site at the other

• There are nine hydrogen bonds (tertiary hydrogen bonds) that help 3-D structure of tRNA molecules. They mainly involve base pairing between several invariant bases

tRNA – 3D Structure

There are nine bonds in tRNAtertiary structure:

Two are formed between DHU loop and TψC loop involving which G*=ψ and G=C respectively.

One within the TψC loop between T=A*.

One within anticodon loop between Y and purine.

The rest of the five bonds involve DHU arm; three of which are formed between the DHU arm and variable arm and two occur within the DHU loop

tRNA Molecule

• rRNA is a component of the ribosomes where translation (protein synthesis) is occurring

• It is the most stable form of RNA and also the type which has got high half life

rRNA

Comparison between prokaryotic and eukaryotic rRNA

Prokaryotic Ribosome(2.7 x 106)

Eukaryotic Ribosome (4.2 x 106)

50S (1.8 x 106) 30S (0.9 x 106) 60S (2.8 x 106) 40S (1.4 x 106)

5S & 23S rRNA36 proteins

16s rRNA21 proteins

5S, 28S & 5.8S rRNA~49 proteins

18s rRNA~33 proteins

rRNA

• Another type of RNA in eukaryotic cells, called snRNA (for small nuclear RNA) helps process some RNAs after they are made

• Many eukaryotic RNAs have portions of them removed by a process called splicing. It is this process in which the snRNAs participate

snRNA

• An RNA virus is a virus that has RNA (ribonucleic acid) as its genetic material

• This nucleic acid is usually

• single-stranded RNA (ssRNA)

• double-stranded RNA (dsRNA)

Viral RNA

Viral RNA

Viral RNA

Questions?

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