Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Oct;28(10):793-806.
doi: 10.1016/j.tcb.2018.05.006. Epub 2018 Jun 19.

Tie-Break: Host and Retrotransposons Play tRNA

Andrea J Schorn  1 , Rob Martienssen  2
Affiliations
Review

Tie-Break: Host and Retrotransposons Play tRNA

Andrea J Schorn et al. Trends Cell Biol. 2018 Oct.

Abstract

tRNA fragments (tRFs) are a class of small, regulatory RNAs with diverse functions. 3'-Derived tRFs perfectly match long terminal repeat (LTR)-retroelements which use the 3'-end of tRNAs to prime reverse transcription. Recent work has shown that tRFs target LTR-retroviruses and -transposons for the RNA interference (RNAi) pathway and also inhibit mobility by blocking reverse transcription. The highly conserved tRNA primer binding site (PBS) in LTR-retroelements is a unique target for 3'-tRFs to recognize and block abundant but diverse LTR-retrotransposons that become transcriptionally active during epigenetic reprogramming in development and disease. 3'-tRFs are processed from full-length tRNAs under so far unknown conditions and potentially protect many cell types. tRFs appear to be an ancient link between RNAi, transposons, and genome stability.

Keywords: LTR-retrotransposon; primer binding site; retrovirus; small RNA; tRF; tRNA.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.. Reverse Transcription of LTR-Retrotransposons and -Viruses.
Long terminal repeats (LTR) encode promoter elements and termination signals. The RNA transcript contains a region repeated at either end (R), a segment unique to the 5’ end of the RNA (U5), and a segment only included at the 3’-end of the RNA (U3). The 3’-end of cellular tRNAs (red cloverleaf) primes reverse transcription by hybridizing to the primer binding site (PBS). While this segment is being copied into first-strand cDNA (brown line), also called (−)ssDNA (minus strong stop DNA), the RNaseH activity of RT degrades the template RNA. The elongating cDNA is transferred to the 3’-end of the retrotransposon transcript by hybridizing to the R region. The remaining RNA is partially degraded by RNaseH leaving behind primers for second-strand cDNA synthesis. After another transfer event, first- and second-strand synthesis are completed to result in a full-length, double-stranded retroviral DNA that will be integrated into the host genome.
Figure 2.
Figure 2.. Model of LTR-Retroelement Silencing by 3’-tRFs.
LTR-retroelements comprise LTR-retrotransposons and LTR-retroviruses. In the absence of epigenetic suppression, non-coding and coding LTR-retroelements are transcribed. Elements that encode the enzymatic machinery for retroviral replication are autonomous and in the first step their RNA is spliced and translated. 22 nt 3’-tRFs (tRF3-b) target coding-competent LTR-retroelements at the level of retroviral protein production through post-transcriptional gene silencing. Retroviral gene products of the autonomous, coding element constitute all components of the retroviral particle and recruit virus “genomic” unspliced RNA template of both coding and non-coding family members as well as host-dependent co-factors like tRNAs to the particle. 18 nt 3’-tRFs (tRF3-a) interfere with reverse transcription at the level of first-strand synthesis and therefore inhibit both coding and noncoding, non-autonomous retrotransposons. 3’-tRFs specifically promote silencing of any potentially mobile LTR-retroelement that has maintained a functional PBS. PBS, primer binding site; RT, reverse transcriptase.
Figure 3.
Figure 3.. tRNA Structure and Domains
Three alternative representations of the same tRNA, here of tRNA Lys-AAA with the anticodon-sequence UUU, illustrate its functional domains and tertiary structure. (A) The typical cloverleaf diagram provides an overview of the major domains and loops. The acceptor stem has the post-transcriptional CCA-tag at its 3’-end that will be covalently linked with the amino-acid prior to translation. (B) The three-dimensional L-shaped structure of tRNA is composed of two double-stranded helices: (C) the anticodon-D-loop (black/grey) that serves proof-reading functions during translation at the ribosome and the upper minihelix (green) consisting of the acceptor-stem and the TψC-loop. (Figure modified from [58]).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kumar P et al. (2016) Biogenesis and Function of Transfer RNA-Related Fragments (tRFs). Trends Biochem Sci 41 (8), 679–89. - PMC - PubMed
    1. Peaston AE et al. (2004) Retrotransposons regulate host genes in mouse oocytes and preimplantation embryos. Dev Cell 7 (4), 597–606. - PubMed
    1. Feschotte C (2008) Transposable elements and the evolution of regulatory networks. Nat Rev Genet 9 (5), 397–405. - PMC - PubMed
    1. Faulkner GJ et al. (2009) The regulated retrotransposon transcriptome of mammalian cells. Nat Genet 41 (5), 563–71. - PubMed
    1. Siomi MC et al. (2011) PIWI-interacting small RNAs: the vanguard of genome defence. Nat Rev Mol Cell Biol 12 (4), 246–58. - PubMed

Publication types