High impact information on SMG6

• Here we show that SMG5 and SMG7 colocalize in cytoplasmic mRNA decay bodies, while SMG6 forms separate cytoplasmic foci [1].
• SMG6 and SMG5 are essential factors in nonsense-mediated mRNA decay, a conserved pathway that degrades mRNAs with premature translation termination codons [2].
• Intriguingly, SMG1 and EST1A/SMG6 function also in DNA repair and telomere maintenance, respectively [3].
• Overproduction of hEST1A cooperated with hTERT to lengthen telomeres, an effect that was specific to cells containing telomerase activity [4].
• One of three human homologs, designated human EST1A (hEST1A), is shown to be associated with most or all active telomerase in HeLa cell extracts [5].
• As for the biological role of Smg6, a recent paper [6] showed that complete loss of Smg6 causes mouse lethality at the blastocyst stage. However, inducible deletion of Smg6 is compatible with embryonic stem cell (ESC) proliferation despite the absence of telomere maintenance and functional NMD.  Differentiation of Smg6-deficient ESCs is blocked due to sustained expression of pluripotency genes, normally repressed by NMD, and forced down-regulation of one such target, c-Myc, relieves the differentiation block. 
• Smg6-null embryonic fibroblasts (MEFs) are viable as well, but are refractory to cellular reprograming into induced pluripotent stem cells (iPSCs) [6].

Biological context of SMG6

• Thus, overexpression of hEST1A affects telomere capping [5].
• Overexpression of hEST1A induces anaphase bridges due to chromosome-end fusions, and telomeric DNA persists at the fusion points [5].

Analytical, diagnostic and therapeutic context of SMG6

• Crystallization and preliminary X-ray analysis of the PIN domain of human EST1A [7].

References