Transposons are DNA sequences that can move within genomes. There are two main categories: DNA transposons, which use a cut-and-paste mechanism, and retrotransposons, which use a copy-and-paste mechanism. Barbara McClintock discovered the first transposable element in maize in the 1940s. DNA transposons have been found in bacteria and eukaryotes, while retrotransposons are more common in eukaryotes. Retrotransposons include LTR retrotransposons and non-LTR retrotransposons such as LINEs and SINEs, which account for a large percentage of the human genome. Transposition mechanisms involve RNA transcription, reverse
2. Transposon
DNA sequence that can move in the genome
Also called mobile DNA element or transposable element
“selfish DNA”--exist only to maintain themselves ?
Transposition: The process by which these sequences are
copied and inserted into a new site in the genome
Probably had a significant influence on evolution
3. How transposon was found
1940s, Barbara McClintock discovered the
first transposable element in maize, earned a
Nobel prize in 1983.
Late 1960s, transposition was also found in
Bacteria.
Barbara McClintock
4. Two Categories
DNA transposons
Retrotransposons
“cut-and-paste”
Most mobile elements in bacteria is
DNA transposons
In contrast, most mobile elements
in eukaryotes are retrotransposons,
but eukaryotic DNA transposons
also occur.
“copy-and-paste”
7. General structure of eukaryotic LTR retrotransposons
Retrotransposons
LTR retrotransposons:
Non-LTR retrotransposons: the most common type of transposons in mammals
What is the difference from retrovirus?
10. Retrotransposons
• Non-LTR retrotransposons
long interspersed elements (LINEs)
≈6 kb in human
account for 21% of the genome
short interspersed elements (SINEs)
≈300 bp in human
account for 13% of the genome
13. Most are tRNA derived; Alu is 7SL-RNA
Nonautonomous
Dependent on other machinery- genome
“parasite”
RNA Pol III
Needs LINE Endonuclease and Reverse
Transcriptase for activity
14. Average size 150-200 base pairs
Composed of 3 parts
5’ head
Body
3’ tail
21. Where there is a SINE, there is a LINE
Specificity of EN/RT of LINE dictates
location
Expressed during early embryogenesis and
decreases in development
Active in tumor cells
Integrates into germ lines
LTR retrotransposons encode all the proteins of the most common type of retroviruses, except for the envelope proteins. Lacking these envelope proteins, LTR retrotransposons cannot bud from their host cell and infect other cells; however, they can transpose to new sites in the DNA of their host cell.
Non protein encoded regions, related to tRNA (except Alu-7SL RNA)
Nonautonomous- does not encode own machinery, instead relies on cell machinery (Pol III) and LINES RT/EN complex
Found in CpG regions
5’head region is related to tRNA, has type 2 promoter, specfic for tRNA, is internal and has 2 short sequences A and B (promoter regions)
Its function is for initiation, regulation and aid in transport to cytoplasm
Body-tRNA unrelated. 3’ end of the body is similar to 3’ end of LINE- needed for RT
3’Tail-AT rich or repeats; poly T tail- termination signal for Pol III
Function-termination and delievery to LineRT
Alu exampleLeft and right connected by A rich regions
Pol III binds to TRIIIB to DNA and recruits Pol III complex, terminated by U’s
Dependent on upstream cis factors-could inhibit transcription
Not much is known about the mechanism of transport to cytoplasm
Theory is that it uses RanGTP-independent mRNA pathway
Needs an “A” rich tail
No introns
Caps not required
Nuclear Import
Importins, are proteins that bind NLS
RT-Uses LINE Machinery
Alu gene for example
RNA binds by 2 SRP proteins (SRP9 and SRP14)
Binds ribosome translating L1 RNA and presents A tail to RT where it is recognized and transcribed
Due to repeats seen in SINEs (conserved), RT can jump from 1 template to another.Jumps backwards-duplicated
Jumps forward-deleted
What happens when inserted?Usually inserts in Introns, ends, other non coding regions. But if spicesome recognizes SINE as exon, spliced out and create a new gene-can be harmful or beneficial. Genetic disorders (such as hemophila ) or cancer (breast) results in SINE disrupting
Found in GC rich areas-highly methylated so turned off
Be enhancers/silencers, encoded into genome, splice out, etc