14.8: Mechanisms of Retrotransposition
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\(\newcommand{\avec}{\mathbf a}\) \(\newcommand{\bvec}{\mathbf b}\) \(\newcommand{\cvec}{\mathbf c}\) \(\newcommand{\dvec}{\mathbf d}\) \(\newcommand{\dtil}{\widetilde{\mathbf d}}\) \(\newcommand{\evec}{\mathbf e}\) \(\newcommand{\fvec}{\mathbf f}\) \(\newcommand{\nvec}{\mathbf n}\) \(\newcommand{\pvec}{\mathbf p}\) \(\newcommand{\qvec}{\mathbf q}\) \(\newcommand{\svec}{\mathbf s}\) \(\newcommand{\tvec}{\mathbf t}\) \(\newcommand{\uvec}{\mathbf u}\) \(\newcommand{\vvec}{\mathbf v}\) \(\newcommand{\wvec}{\mathbf w}\) \(\newcommand{\xvec}{\mathbf x}\) \(\newcommand{\yvec}{\mathbf y}\) \(\newcommand{\zvec}{\mathbf z}\) \(\newcommand{\rvec}{\mathbf r}\) \(\newcommand{\mvec}{\mathbf m}\) \(\newcommand{\zerovec}{\mathbf 0}\) \(\newcommand{\onevec}{\mathbf 1}\) \(\newcommand{\real}{\mathbb R}\) \(\newcommand{\twovec}[2]{\left[\begin{array}{r}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\ctwovec}[2]{\left[\begin{array}{c}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\threevec}[3]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\cthreevec}[3]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\fourvec}[4]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\cfourvec}[4]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\fivevec}[5]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\cfivevec}[5]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\mattwo}[4]{\left[\begin{array}{rr}#1 \amp #2 \\ #3 \amp #4 \\ \end{array}\right]}\) \(\newcommand{\laspan}[1]{\text{Span}\{#1\}}\) \(\newcommand{\bcal}{\cal B}\) \(\newcommand{\ccal}{\cal C}\) \(\newcommand{\scal}{\cal S}\) \(\newcommand{\wcal}{\cal W}\) \(\newcommand{\ecal}{\cal E}\) \(\newcommand{\coords}[2]{\left\{#1\right\}_{#2}}\) \(\newcommand{\gray}[1]{\color{gray}{#1}}\) \(\newcommand{\lgray}[1]{\color{lightgray}{#1}}\) \(\newcommand{\rank}{\operatorname{rank}}\) \(\newcommand{\row}{\text{Row}}\) \(\newcommand{\col}{\text{Col}}\) \(\renewcommand{\row}{\text{Row}}\) \(\newcommand{\nul}{\text{Nul}}\) \(\newcommand{\var}{\text{Var}}\) \(\newcommand{\corr}{\text{corr}}\) \(\newcommand{\len}[1]{\left|#1\right|}\) \(\newcommand{\bbar}{\overline{\bvec}}\) \(\newcommand{\bhat}{\widehat{\bvec}}\) \(\newcommand{\bperp}{\bvec^\perp}\) \(\newcommand{\xhat}{\widehat{\xvec}}\) \(\newcommand{\vhat}{\widehat{\vvec}}\) \(\newcommand{\uhat}{\widehat{\uvec}}\) \(\newcommand{\what}{\widehat{\wvec}}\) \(\newcommand{\Sighat}{\widehat{\Sigma}}\) \(\newcommand{\lt}{<}\) \(\newcommand{\gt}{>}\) \(\newcommand{\amp}{&}\) \(\definecolor{fillinmathshade}{gray}{0.9}\)There are two mechanisms of retrotransposition. They are extrachromosomally primed retrotransposition (seen in e.g., LTR retrotransposons) and insertion-target-site-primed retrotransposition (seen in non-LTR retrotransposons like LINEs and SINEs). We will consider these two mechanisms next.
14.8.1 Extrachromosomally Primed Retrotransposition (e.g., of a LINE)
As its name suggests, in extrachromosomally primed retrotransposition, a separate circular reverse transcript of the retrotransposon attacks, nicks, and integrates into a genomic insertion site (Figure 14.23). In this mechanism, reverse transcriptase creates a cDNA copy of a transcribed retro-element. Integrase-endonuclease then binds the cDNA copy, holding the ends together, in effect circularizing it. This isolable ribonucleoprotein resembles an intasome, a structure similar to the nucleoprotein complex that catalyzes integration of retroviral cDNAs during lysogeny. The 3D structure of a retroviral intasome interacting with DNA and nucleosomes was recently determined (for more, see Retroviral Intasome 3D Structure). In this form, the retrotransposon attacks DNA at an insertion site, creating staggered ends. After insertion, the gaps in the DNA are filled in. Ligation seals the retrotransposon into its new location, creating direct insertion-site repeats.
14.8.2 Target-Site Primed SINE Retrotransposition (e.g., of a SINE)
In target-site primed retrotransposition (retroposition) of a SINE, RNA polymerase III (the same enzyme that catalyzes tRNA and 5S rRNA transcription) transcribes the SINE. If a LINE is concurrently transcribed, its enzymes will be made. When its integrase-endonuclease catalyzes hydrolysis of one strand of DNA at a new insertion site, the 3’ OH end of this strand can prime reverse transcription of the one SINE cDNA strand by the LINE reverse transcriptase. After hydrolysis of the second target-site DNA strand, its 3’ OH end primes replication of the second strand of the SINE cDNA. Integrase then completes insertion of the copy-SINE into its new genomic location.
The key feature of target site-primed retrotransposition (retroposition) is the absence of an integrase-bound, separate, circular, double-stranded reverse transcript (Figure 14.24).
