| 2015 |
HENMT1 is required for 2'-O-methylation of the 3'-terminal nucleotide of mammalian piRNAs; loss of HENMT1 leads to piRNA instability, reduced piRNA bulk and length, transposable element de-repression in adult meiotic and haploid germ cells, and male sterility characterized by germ cell arrest at the elongating spermatid phase. |
Mouse loss-of-function model, RNA-Seq, RNA assays (piRNA length/abundance measurement, TE expression assays) |
PLoS genetics |
High |
26496356
|
| 2021 |
HENMT1-mediated piRNA stabilization (via 3'-terminal 2'-O-methylation) is required for normal female fertility; Henmt1 mutant females show 3- to 4-fold reduction in follicle number, reduced litter sizes, meiosis-II spindle abnormalities, and a dramatically altered oocyte transcriptome including down-regulation of microtubule function transcripts. |
Henmt1 mutant mouse model, follicle counting, spindle imaging, transcriptome analysis |
Molecular human reproduction |
High |
34590701
|
| 2020 |
HENMT1 is identified as the methyltransferase responsible for 3'-terminal 2'-O-methylation of mammalian miRNAs (demonstrated for miR-21-5p in lung cancer); methylated miR-21-5p shows increased resistance to 3'→5' exoribonuclease PNPT1 and higher affinity for Argonaute-2, resulting in greater stability and stronger translational repression of PDCD4. |
LC-MS/MS, qRT-PCR, northern blot with oxidation/β-elimination, PNPT1 digestion assay, Argonaute-2 binding assay, PDCD4 reporter assay |
Nucleic acids research |
High |
32542340
|
| 2020 |
In the piRNA biogenesis pathway, Zucchini-dependent cleavage of pre-pre-piRNAs is accompanied by 2'-O-methylation by Hen1 (HENMT1 ortholog), and pre-piRNAs are matured by Trimmer and Hen1 regardless of the endonucleolytic mechanism (Zucchini-dependent or slicing-dependent), placing HENMT1 at the final maturation step of piRNA processing. |
Trimmer-knockout silkworm cell line, cell-free reconstitution system recapitulating Zucchini-mediated cleavage, biochemical fractionation |
Nature |
High |
31996847
|
| 2017 |
HENMT1 and PIWIL1 are co-expressed in pachytene spermatocytes and spermatids in human testis; HENMT1-overexpressing TCam2 seminoma cells show lower LINE-1 transposon expression, supporting a conserved transposon-repressing function of HENMT1 in adult human testis. |
Immunolocalization, RT-PCR after laser microdissection, RT-qPCR on 222 testis biopsies, stable HENMT1-overexpressing cell line assay |
Reproduction (Cambridge, England) |
Medium |
28676534
|
| 2024 |
Computational modeling of the HENMT1 catalytic mechanism indicates that Mg2+ is coordinated by four evolutionarily conserved residues plus the 3'-O and 2'-O of the terminal piRNA nucleotide; the reaction involves deprotonation of 2'-OH (potentially by His800 and Asp859) followed by methyl transfer from SAM to the 2'-O; Mg2+ is required for catalysis but not for substrate/cofactor binding. |
Computational modeling (molecular dynamics, quantum mechanics/molecular mechanics), evolutionary conservation analysis |
PloS one |
Low |
38198468
|
| 2024 |
A homozygous nonsense variant in HENMT1 (c.555G>A, p.Trp185*) causes non-obstructive azoospermia in a human patient; mouse models carrying the equivalent variant display spermiogenesis arrest, significant LINE1 retrotransposon de-repression in testes, and increased spermatid apoptosis, establishing HENMT1 loss-of-function as directly causative of human male infertility. |
Whole-exome sequencing, Sanger sequencing, in vivo mouse model mimicking patient mutation, retrotransposon expression assay, TUNEL/apoptosis assay |
Andrology |
High |
39318356
|
| 2025 |
HENMT1 methylates the 3'-ends of tRNA-derived small RNA fragments (3'-tRFs), protecting them from degradation and non-templated tailing by TUT4 and TENT2; 3'-tRFs with perfect complementarity to endogenous retroviral sequences silence ERV activity, and HENMT1 loss leads to reduced 3'-tRF stability and increased ERV activity, extending HENMT1's transposon-silencing role to somatic cells via a piRNA-independent mechanism. |
HENMT1 knockout cells, small RNA sequencing, massively parallel reporter assay (ERV target rules), 2'-O-methylation detection, TUT4/TENT2 tailing assay |
bioRxivpreprint |
Medium |
40463248
|
| 2025 |
A homozygous frameshift variant in HENMT1 (c.47_75del, p.F16Sfs*3) was identified in a patient with non-obstructive azoospermia; testicular tissue from this patient showed reduced abundance of piRNAs, corroborating HENMT1's role in piRNA stabilization in humans. |
Whole-exome sequencing, Sanger sequencing, small RNA sequencing of testicular tissue |
Reproductive biomedicine online |
Medium |
40645105
|