Nucleic Acid 3 Flashcards
There are only 4 bases commonly found in DNA/RNA:
A, C, G, T/U
So have some common “motifs” (sequences of bases).
Palindromes:
- read same in both directions,
e.g. ROTATOR
- In DNA are really “inverted repeats”
Note: self-complementary sequences within strands
What About Base Sequence?
If the inverted repeat is within one individual
strand, it’s called a mirror repeat:
Self-complementary sequences within each single strand of DNA or a strand of RNA can form intra- strand H bonds between complementary bases…
What are Hairpins?
- Hairpins form when a SINGLE DNA or RNA strand FORMS BASE PAIRS:
- ISOLATED DNA SOLUTIONS with
such SEQUENCES
can FORM COMPLEX
STRUCTURES WITH MULTIPLE HAIRPINS. - Note: base-pairs within strands are ANTIPARALLEL
What is CRUCIFORM?
- When BOTH STRANDS of
DNA are involved, in
INTRA-STRAND H bonding,
get a CRUCIFORM. - Cruciform DNA has
been found in some
BACTERIA, but not (yet?)
in human cells.
What is RNA? = 4
- RNA is INTERMEDIARY in CONVERTING GENETIC INFORMATION INTON THE PRODUCTION OF FUNCTIONAL PROTEINS….
- SECOND MAJOR FORM OF NUCLEIC ACID IN CELLS.
- In eukaryotes, DNA = NUCLEUS;
whereas RNA = NUCLEUS AND CYTOPLASM. - Since 1950’s thought RNA had role as a MESSENGER & INFORMATION RELAY FROM THE NUCLEUS TO THE CYTOPLASMrelay from the nucleus to the cytoplasm
RNA – polymer of ribonucleotides
EXPLAIN THE RNA PRIMARY STRUCTURE:
- Polymer of
ribonucleotides, joined
by POSPHODIESTER BONDS - Sugar = ribose
- Uracil replaces the
thymine found in DNA - RNA = SINGLE STRANDED
Understanding RNA primary Structure…..3
- same as DNA primary structure
- sequence of
ribonucleotides from 5’ to 3’ - Many RNAs have SEQUENCES THAT ENABLE FORMATION OF INTRA-STRAND COMPLEMENTARY BASE PAIRS…
Understanding RNA Secondary Structure
- RNA is synthesised as a SINGLE STRAND BUT this
does NOT mean RNA has a RANDOM STRUCTURE. - Single strands tend to make up a RIGHT-HANDED HELIX DOMINATED BY BASE-STACKING INTERACTIONS, WITH
*****PURINE-PURINE STACKS BEING THE STRONGEST. - RNA can for INTRA-STRAND H BONDS AND MANY RNAs have COMPLEX SECONDARY STRUCTURES, ENABLING VARIOUS FUNCTIONS THAT RNAs perform.
RNA Secondary Structure - Self-complementary sequences can lead to….
- RNA Secondary Structure - Self-complementary sequences can lead to COMPLEX AND SPECIFIC STRUCTURES.
- RNA can Base pair complementary strands of DNA or RNA….
- Standard base pairs C:G, A:T or A:U and ANTIPARALLEL.
- single strand, bulge, internal loop, hairpin
Uracil rather than Thymine
CHEMICAL DIFFERENCE does NOT IMPACT U-A base-pairing.
Important for transcription of RNA (DNA:RNA hybrid).
But uracil CAN BASE PAIR with OTHER RIBONUCLEOTIDES INCLUDING ITSELF. ….
Explain RNA STRUCTURE is Essential to FUNCTION….
- RNA can BASE PAIR CONVENTIONALLY (A-U & G-C),
& also UNUSUAL base-pairing such as U-U or G-U
2.The unusual base pairings = RNAs to form EXTENSIVE, COMPLICATED STRUCTURES.
3.Note: H bonds in U-G/U-U are WEAKER than those in U-A.
4.FOLDED RNA can have
ENZYMATIC ACTIVITY (ribozyme) & various STRUCTURAL ROLES.
RNA grouped into two “classes”
1.CODING: Encodes PROTEIN PRIMARY STRUCTURE
—- mRNA (messenger) “code”.
- NONCODING: Functional RNAs, i.e. RNA itself is
the final functional product
- tRNA (transfer) - “one” for each AA
- rRNA (ribosomal) - part of ribosomes
Majority of RNAs are Noncoding…
Majority of RNAs are Noncoding
mRNA
Messenger RNAs = code for Protein
rRNA
Ribosomal RNA, form the
- basic structure of the ribosome and
- catalyze protein synthesis
tRNA
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 spicing of pre-mRNA.
These 3 RNA types are essential FOR
PROTEIN SYNTHESIS
Noncoding snRNAs are essential for
JOINING EXONS
Transfer RNAs deliver amino acids to the
ribosome (where proteins are made)
— AA attachment is very specific & is at the 3’-OH of the tRNA.
—- Single stranded tRNA = “cloverleaf” structure of “hairpins”.
—- Four double-helical stems & three single stranded loops.
Why does DNA have deoxyribose?
- RNA in solution with
high pH … ionisation
of OH; eventually
forming 2’,3’-cyclic
mono-nucleotides. - In contrast: alkali is an
excellent denaturant
for DNA.
Why have DNA and RNA??
- DNA is more stable & less reactive than RNA
= a better long term genetic store! - The GROOVES in RNA LARGER than in DNA, allowing ACCESS to DEGRADING ENZYMES, so RNA isLESS STABLE than DNA.
- DEOXYRIBOSE in SUGAR-PHOSPHATE backbone MORE STABLE = greater length.
- DOUBLE HELIX & THYMINE instead of URACIL= STABLE &
errors during replication
easier to RECOGNISE/REPAIR.
Hypothesis – RNA preceded DNA & proteins in evolution
- If nucleic acids needed to synthesise proteins & proteins in turn required to synthesise nucleic acids – how did
interdependent components arise? - Maybe RNA both stored genetic material & catalysed chemical reactions, only later did DNA take over as genetic material & proteins become major catalyst & structural component
of cells… - Do RNAs with catalytic activity in modern day cells – yes! Ribozymes for example rRNA catalyses peptide bond formation!
DNA, RNA & Protein Sequences = 5
- DNA = two strands
- RNA only ONE, but
can have VERY COMPLEX STRUCTURES… - DNA is TRANSCRIBED
into RNA - RNA is TRANSLATED
into PROTEIN - GENE EXPRESSION is
an important FUNCTION OF NUCLEIC ACIDS.
GENE
- A gene is the basic unit of heredity
- Genes are segments of DNA (so, double stranded!).
- Genes define the sequence of proteins & RNAs.
All RNAs are transcribed from DNA….
- some are then further processed through translation to form proteins.
- So, while some genes are transcribed into mRNAs (which encode protein amino acid sequence), other
genes are not (these genes are for functional RNAs).
GENOME
The genome is all the genetic information of an
organism
(in humans this is the total amount of DNA in
our chromosomes…).
CHROMOSOME
Each chromosome is a single DNA molecule, a double helix (double-stranded DNA).
Chromosomes can be LINEAR OR CIRCULAR!
The length of DNA =
how many base pairs (bp) it contains.
The total amount of DNA in the chromosomes of a cell (genome) varies between species:
- Human genome ~ 3,100,000 kbp = 3.1 billion bp.
46 linear chromosomes in the nucleus plus circular
mitochondrial chromosome.
Nuclear DNA is associated with histone
proteins to form chromatin. During cell
division = supercondensed chromosomes.
- E coli (bacteria) genome ~ 4600 kbp (kilobase pairs) in a single, circular chromosome.
- Human genome ~ 3,100,000 kbp = 3.1 billion bp.
- 46 linear chromosomes in the nucleus plus circular
mitochondrial chromosome. - Nuclear DNA is associated with histone
proteins to form chromatin. - During cell
division = supercondensed chromosomes.
Histones =
- most abundant proteins in nuclear chromatin.
- Histone “tails” are rich in +vely charged (basic) amino acids.
Why do histone proteins associate with DNA?
Histone proteins can be
modified by adding or
removing phosphate or
acetyl groups… neutralise
the +ve charges!
Note – mitochondrial DNA
does not bind histones.
Histone Modification:
- Consider addition of acetyl (CH3C=O- ) groups to lysine residues = acetylation.
- Catalysed by acetyltransferases.
3.Acetylation of histone proteins weakens their interactions with DNA & thus increases accessibility of genes, so RNA
can be transcribed.
- Deacetylases strip off the acetyl groups, thus restoring chromatin structure
Karyotype -
MALE HUMAN =
- 22 pairs of
autosomes,
plus two “sex”
chromosomes
one X, one Y
Changes to DNA composition can result in vastly different
characteristics (phenotype)
Nuclear Chromosomes:
Each species has a unique chromosome complement -
shape, size & number… which doesn’t relate to size &
complexity: crocodile - 64, carp - 100! Humans - 46
Trisomy 21
- imbalance between the number of genes on all the other chromosomes & that on chr 21, no longer a 1:1 ratio …
- An extra chromosome 21
47 chromosomes in total - Gene balance changed… this person has more chr 21 genes (more RNAs & proteins), compared to all the other genes in this person’s genome.
Gene Balance Impacts Phenotype….
NORMALPHYSIOLOGY RELIES ON GENE BALANCE…
, if this is
NOT MAINTAINED = IMBALANCE IN CELLULAR PATHWAYS
—–this is particularly important during development.
- In a trisomy, the person’s phenotype results from the combination of all the imbalances of the genes on the chromosome that there is an extra copy of.
- The ratio of genes altered.
The RATIO OF GENE PRODUCTS (RNAs & proteins) ALTERED
= CHANGES IN PHENOTYPE (characteristics)
