Ambros became a faculty member atHarvard University in 1984. However, Harvard denied tenure to Ambros shortly after he discovered what is now known as microRNA.[10] About this, Baltimore later said in 2008: "They lost a potential Nobel laureate because they simply didn't see in him the potential that he had ... It's the nature of a seminal discovery that it's seminal in retrospect. You can't know ahead of time."[10]
Ambros joined the faculty ofDartmouth College in 1992.[9] He joined the faculty at theUniversity of Massachusetts Medical School in 2008, and currently holds the title of Silverman Professor of Natural Sciences in the program in Molecular Medicine, endowed by his former Dartmouth student, Howard Scott Silverman.[2][9][11]
In 1993, Ambros and his co-workersRosalind Lee andRhonda Feinbaum[12] reported in the journalCell[13] that they had discovered single-stranded non-protein-coding regulatoryRNA molecules in the organismC. elegans. Previous research, including work by Ambros and Horvitz,[14][15] had revealed that a gene known aslin-4 was important for normal larval development ofC. elegans, a nematode often studied as a model organism. Specifically,lin-4 was responsible for the progressive repression of the proteinLIN-14 during larval development of the worm; mutant worms deficient inlin-4 function had persistently high levels of LIN-14 and displayed developmental timing defects.[15]
Ambros and colleagues found thatlin-4, unexpectedly, did not encode a regulatory protein. Instead, it gave rise to some small RNA molecules, 22 and 61 nucleotides in length, which Ambros called lin-4S (short) and lin-4L (long). Sequence analysis showed that lin-4S was part of lin-4L: lin-4L was predicted to form a stem-loop structure, with lin-4S contained in one of the arms, the 5' arm. Furthermore, Ambros, together withGary Ruvkun (Harvard), discovered that lin-4S was partially complementary to several sequences in the 3' untranslated region of the messenger RNA encoding the LIN-14 protein.[16] Ambros and colleagues hypothesized and later determined thatlin-4 could regulate LIN-14 through binding of lin-4S to these sequences in thelin-14 transcript in a type of antisense RNA mechanism.[17]
In 2000, anotherC. elegans small RNA regulatory molecule,let-7, was characterized by the Ruvkun lab[18] and found to be conserved in many species, including vertebrates.[19] These discoveries, among others, confirmed that Ambros had in fact discovered a class of small RNAs with conserved functions, now known asmicroRNA.[20]
Ambros was elected to theUnited States National Academy of Sciences in 2007.[21] He was elected a Fellow of the American Academy of Arts and Sciences in 2011.[22] In 2024 he shared the Nobel Prize in Physiology and Medicine with Gary Ruvkun "for the discovery of microRNA and its role in post-transcriptional gene regulation".[2]
^Reinhart, B. J.; Slack, F. J.; Basson, M.; Pasquinelli, A. E.; Bettinger, J. C.; Rougvie, A. E.; Horvitz, H. R.; Ruvkun, G. (2000). "The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans".Nature.403 (6772):901–906.Bibcode:2000Natur.403..901R.doi:10.1038/35002607.PMID10706289.S2CID4384503.
^Pasquinelli, A. E.; Reinhart, B. J.; Slack, F.; Martindale, M. Q.; Kuroda, M. I.; Maller, B.; Hayward, D. C.; Ball, E. E.; Degnan, B.; Müller, B.; Spring, P.; Srinivasan, J. R.; Fishman, A.; Finnerty, M.; Corbo, J.; Levine, J.; Leahy, M.; Davidson, P.; Ruvkun, E. (2000). "Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA".Nature.408 (6808):86–89.Bibcode:2000Natur.408...86P.doi:10.1038/35040556.PMID11081512.S2CID4401732.
