Junk in Your Genome: SINES

In a previous posting I talked about Long Interspersed Elements or LINEs [Junk in Your Genome: LINEs]. These are retrotransposons that make up a significant percentage of the junk DNA in your genome. Most of them are completely defective, they are incapable of transposing and they usually don't encode any functional proteins.

THEME

Genomes & Junk DNA
A minority of LINEs are still active. Their genes for reverse transcriptase and endonuclease are still functional and the the transposons still retain the end sequences necessary for insertion.

Today I want to discuss Short Interspersed Elements or SINEs. These pieces of DNA tend to be only 100-400 bp in length but they contain all the features of transposons at their ends. The most important of these features is a short repeat of genomic DNA.

Most SINEs are related to the genes for small RNAs and, more specifically, to genes that are transcribed by RNA polymerase III [Transcription of the 7SL Gene]. Recall that one of the characteristics of Class III genes is that many of them have internal promoters. What this means is that the start site for transcription lies entirely within the DNA that's transcribed.

SINEs look like this:

The blue line represents the transcribed region of the SINE and the black line is the genomic DNA flanking the insert. At each end there is a short (about 5 bp) direct repeat representing the remnants of the insertion event. The 3′ end of the SINE has a short stretch of adenlyate residues (poly A) that is required for mobility.

A typical SINE is only about 100-400 bp long. As mentioned above, one of the key features of SINEs is the presence of an internal promoter to which RNA polymerase III binds. Class III promoters generally have two separate binding regions designated Box A and Box B. All SINEs are derived from genes encoding cellular RNAs such as tRNA, 7SL RNA, U RNAs, etc. These genes are transcribed by RNA polymerase III.

The SINE is transcribed because of the presence of the internal promoter. The transcript may be copied by reverse transcriptase produced from active LINEs in the genome. The DNA:RNA hybrid can be converted to double-stranded DNA and integrated into the genome as a transposable element using the LINE endonuclease. The process is similar to the mechanism that produces processed pseudogenes derived from mRNA but the difference is that the SINEs can still be transcribed when they have integrated into the genome whereas the mRNA pseudogenes have been separated from their promoter.

In the mouse genome there are two large families of SINEs. The B1 family is derived from a truncated and rearranged 7SL RNA. (Recall that 7SL RNA is the RNA component of signal recognition particle.) The B2 family comes from a tRNA that has acquired a terminal extension (Dewannieux and Heidmann 2005).

Each mouse family has about one million copies and together they make up about 20% of the mouse genome. Most of these transposable elements are defective because they have acquired mutations. They are not mobile and many are not transcribed.

In humans, the largest family of SINEs is called Alu elements after the fact that the sequence is cleaved by the restriction endonuclease Alu. These SINEs are also derived from 7SL RNA but the rearrangement is different from that in mouse. (They have a common ancestor.) There are about one million Alu elements in the human genome.

SINEs make up about 13% of the human genome. The largest proportion, by far, is Alu elements but there are small numbers of SINEs derived from other cellular RNAs such as the U RNAs required for splicing and snoRNAs (Garcia-Perez et al. 2007).

SINEs are parasites (selfish DNA). They are not essential for human survival and reproduction, especially the huge majority of SINEs that are defective. Thus, at least 13% of the human genome is clearly junk. The total amount of junk DNA contributed by all transposable elements is 44% of the genome (Kidwell 2005).

---

Dewannieux, M. and Heidmann, T. (2005) L1-mediated retrotransposition of murine B1 and B2 SINEs recapitulated in cultured cells. J. Mol. Biol. 349:241-7 [PubMed]

Garcia-Perez, J.L., Doucet, A.J., Bucheton, A., Moran, J.V. and Gilbert, N. (2007) Distinct mechanisms for trans-mediated mobilization of cellular RNAs by the LINE-1 reverse transcriptase. Genome Res. 17:602-11. [PubMed] [Genome Research]

Kidwell, M. (2005) "Transposable Elements" in The Evolution of the Genome T.R. Gregory ed. Elsevier Academic Press, New York (USA)