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Title: LIN28 Zinc Knuckle Domain Is Required and Sufficient to Induce let-7 Oligouridylation

Authors:
; ; ; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
NCI
OSTI Identifier:
1430351
Resource Type:
Journal Article
Resource Relation:
Journal Name: Cell Reports; Journal Volume: 18; Journal Issue: 11
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Wang, Longfei, Nam, Yunsun, Lee, Anna K., Yu, Chunxiao, Roth, Kira, Chen, Casandra, Ransey, Elizabeth M., and Sliz, Piotr. LIN28 Zinc Knuckle Domain Is Required and Sufficient to Induce let-7 Oligouridylation. United States: N. p., 2017. Web. doi:10.1016/j.celrep.2017.02.044.
Wang, Longfei, Nam, Yunsun, Lee, Anna K., Yu, Chunxiao, Roth, Kira, Chen, Casandra, Ransey, Elizabeth M., & Sliz, Piotr. LIN28 Zinc Knuckle Domain Is Required and Sufficient to Induce let-7 Oligouridylation. United States. doi:10.1016/j.celrep.2017.02.044.
Wang, Longfei, Nam, Yunsun, Lee, Anna K., Yu, Chunxiao, Roth, Kira, Chen, Casandra, Ransey, Elizabeth M., and Sliz, Piotr. Wed . "LIN28 Zinc Knuckle Domain Is Required and Sufficient to Induce let-7 Oligouridylation". United States. doi:10.1016/j.celrep.2017.02.044.
@article{osti_1430351,
title = {LIN28 Zinc Knuckle Domain Is Required and Sufficient to Induce let-7 Oligouridylation},
author = {Wang, Longfei and Nam, Yunsun and Lee, Anna K. and Yu, Chunxiao and Roth, Kira and Chen, Casandra and Ransey, Elizabeth M. and Sliz, Piotr},
abstractNote = {},
doi = {10.1016/j.celrep.2017.02.044},
journal = {Cell Reports},
number = 11,
volume = 18,
place = {United States},
year = {Wed Mar 01 00:00:00 EST 2017},
month = {Wed Mar 01 00:00:00 EST 2017}
}
  • The uridyl transferases TUT4 and TUT7 (collectively called TUT4(7)) switch between two modes of activity, either promoting expression of let-7 microRNA (monoU) or marking it for degradation (oligoU). Lin28 modulates the switch via recruitment of TUT4(7) to the precursor pre-let-7 in stem cells and human cancers. We found that TUT4(7) utilize two multidomain functional modules during the switch from monoU to oligoU. The catalytic module (CM) is essential for both activities, while the Lin28-interacting module (LIM) is indispensable for oligoU. A TUT7 CM structure trapped in the monoU activity staterevealed a duplex-RNA-binding pocket that orients group II pre-let-7 hairpins tomore » favor monoU addition. Conversely, the switch to oligoU requires the ZK domain of Lin28 to drive the formation of a stable ternary complex between pre-let-7 and the inactive LIM. Finally, ZK2 of TUT4(7) aids oligoU addition by engaging the growing oligoU tail through uracil-specific interactions.« less
  • Purpose: Radiotherapy using high linear energy transfer (LET) radiation is aimed at efficiently killing tumor cells while minimizing dose (biological effective) to normal tissues to prevent toxicity. It is well established that high LET radiation results in lower cell survival per absorbed dose than low LET radiation. However, whether various mechanisms involved in the development of normal tissue damage may be regulated differentially is not known. Therefore the aim of this study was to investigate whether two actions related to normal tissue toxicity, p53-induced apoptosis and expression of the profibrotic gene PAI-1 (plasminogen activator inhibitor 1), are differentially induced bymore » high and low LET radiation. Methods and Materials: Cells were irradiated with high LET carbon ions or low LET photons. Cell survival assays were performed, profibrotic PAI-1 expression was monitored by quantitative polymerase chain reaction, and apoptosis was assayed by annexin V staining. Activation of p53 by phosphorylation at serine 315 and serine 37 was monitored by Western blotting. Transfections of plasmids expressing p53 mutated at serines 315 and 37 were used to test the requirement of these residues for apoptosis and expression of PAI-1. Results: As expected, cell survival was lower and induction of apoptosis was higher in high -LET irradiated cells. Interestingly, induction of the profibrotic PAI-1 gene was similar with high and low LET radiation. In agreement with this finding, phosphorylation of p53 at serine 315 involved in PAI-1 expression was similar with high and low LET radiation, whereas phosphorylation of p53 at serine 37, involved in apoptosis induction, was much higher after high LET irradiation. Conclusions: Our results indicate that diverse mechanisms involved in the development of normal tissue damage may be differentially affected by high and low LET radiation. This may have consequences for the development and manifestation of normal tissue damage.« less
  • The activated form of the RecA protein (RecA) is known to be involved in the reactivation and mutagenesis of UV-irradiated bacteriophage lambda and in the expression of the SOS response in Escherichia coli K-12. The expression of the SOS response requires cleavage of the LexA repressor by RecA and the subsequent expression of LexA-controlled genes. The evidence presented here suggests that RecA induces the expression of a gene(s) that is not under LexA control and that is also necessary for maximal repair and mutagenesis of damaged phage. This conclusion is based on the chloramphenicol sensitivity of RecA -dependent repair andmore » mutagenesis of damaged bacteriophage lambda in lexA(Def) hosts.« less
  • Zinc protoporphyrin (ZPP) measurement is a required test under the Occupational Safety and Health Administration's lead standard. However, there is no mention of the influence of hemoglobinopathy on the ZPP test value. We undertook a retrospective laboratory review of 382 employees at the Argonne National Laboratory who had been subjects in a lead surveillance program since 1982. A total of 321 samples were analyzed, after female subjects and samples with abnormally high bilirubin levels were excluded. A group with low mean red blood cell volume (MCV; less than 80.0 fL) was compared with a group with normal MCV (greater ormore » equal to 80.0 fL). A statistically significant difference was noted in ZPP (P < 0.007) and total bilirubin (P< 0.0003) values of two groups. There was no statistically significant difference noted in age, lead levels, or iron levels between the two groups. Abnormally high ZPP levels may occur in individuals with hemoglobinopathies. Only a minor part of this elevation could be explained by the higher bilirubin levels.« less