Ivanov P, O'Day E, Emara MM, Wagner G, Lieberman J, Anderson P. G-quadruplex structures contribute to the neuroprotective effects of angiogenin-induced tRNA fragments. Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):18201-6. Epub 2014 Nov 17 PubMed.
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Royal College of Surgeons in Ireland
The work by Anderson and co-workers really is an exciting and highly interesting finding. We have previously shown that angiogenin is a protective factor for motor neurons (Kieran et al., 2008), so this paper provides new insights into potential mechanisms of action. We also showed that angiogenin is stress-induced and secreted by motor neurons during stress conditions, and then taken up by astrocytes (or endothelial cells). Angiogenin uptake then induces tRNA cleavage in astrocytes (Skorupa et al., 2012)—we proposed that this alters the translational output of astrocytes. Now, the work by Anderson and co-workers suggests another possibility—that there is a paracrine feed-back to motor neurons via G4 secretion and uptake.
On a more cautionary note, some ALS-associated angiogenin mutations have no, or very little loss of, RNase activity, suggesting that the tRNA cleavage is not the only factor involved in angiogenin neuroprotection (or potentially that it is not involved at all).
References:
Kieran D, Sebastia J, Greenway MJ, King MA, Connaughton D, Concannon CG, Fenner B, Hardiman O, Prehn JH. Control of motoneuron survival by angiogenin. J Neurosci. 2008 Dec 24;28(52):14056-61. PubMed.
Skorupa A, King MA, Aparicio IM, Dussmann H, Coughlan K, Breen B, Kieran D, Concannon CG, Marin P, Prehn JH. Motoneurons secrete angiogenin to induce RNA cleavage in astroglia. J Neurosci. 2012 Apr 11;32(15):5024-38. PubMed.
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