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Hall, Ian

Publications and source records attributed to Hall, Ian.

4 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Structure of pre-miR-31 reveals an active role in Dicer–TRBP complex processing

As an essential posttranscriptional regulator of gene expression, microRNA (miRNA) levels must be strictly maintained. The biogenesis of many miRNAs is mediated by trans-acting protein partners through a variety of mechanisms, including remodeling of the RNA structure. miR-31 functions as an oncogene in numerous cancers, and interestingly, its biogenesis is not known to be regulated by protein-binding partners. Therefore, the intrinsic structural properties of the precursor element of miR-31 (pre-miR-31) can provide a mechanism by which its biogenesis is regulated. We determined the solution structure of pre-miR-31 to investigate the role of distinct structural elements in regulating processing by the Dicer–TRBP complex. We found that the presence or absence of mismatches within the helical stem does not strongly influence Dicer–TRBP processing of the pre-miRNAs. However, both the apical loop size and structure at the Dicing site are key elements for discrimination by the Dicer–TRBP complex. Interestingly, our NMR-derived structure reveals the presence of a triplet of base pairs that link the Dicer cleavage site and the apical loop. Mutational analysis in this region suggests that the stability of the junction region strongly influences processing by the Dicer–TRBP complex. Our results enrich our understanding of the active role that RNA structure plays in regulating miRNA biogenesis, which has direct implications for the control of gene expression.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2016

Connecting Paleo and Modern Oceanographic Data to Understand Atlantic Meridional Overturning Circulation Over Decades to Centuries

Modeling is an important tool for understanding AMOC on all timescales. Mechanistic studies of modern AMOC variability have been hampered by a lack of consistency between free-running models and the sensitivity of AMOC to resolution and parameterization. Recent work within the framework of the phase two Coordinated Ocean- Reference Experiments (CORE-II) addresses this issue head on, looking at model differences of AMOC mean state and interannual variability. One consistent feature across the models is that AMOC mean transport is related to mixed layer depths and Labrador Sea salt content, whereas interannual variability is primarily associated with Labrador Sea temperature anomalies. This is consistent with the hypothesized importance of salt balance for AMOC variability on geological timescales. The simulated relationships between AMOC and subsurface temperature anomalies in fully coupled climate models reveal subsurface AMOC fingerprints that could be used to reconstruct historical AMOC variations at low frequency.With the lack of long-term AMOC observations, models of ocean state that assimilate observational data have been explored as a way to reconstruct AMOC, but comparisons between models indicate they are quite variable in their AMOC representations. Karspeck et al. (2015) found that historical reconstructions of AMOC in such models are sensitive to the details of the data assimilation procedure. The ocean data assimilation community continues to address these issues through improved models and methods for estimating and representing error information.Two objectives of paleoclimate modeling are 1) to provide mechanistic information for interpretation of paleoclimate observations, and 2) to test the ability of predictive models to simulate Earth's climate under different background forcing states. In a good example of the first objective, Schmittner and Lund (2015) and Menviel et al. (2014) provided key information about the proxy signals expected under freshwater disturbance of AMOC, which were used to support the paleoclimate observations made by Henry et al. (2016). In an example of the second objective, Muglia and Schmittner (2015) analyzed Third Paleoclimate Modeling Intercomparison Project (PMIP3) models of the Last Glacial Maximum (LGM) and found consistently more intense and deeper AMOC transports relative to preindustrial simulations, counter to the paleoclimate consensus of LGM conditions, indicating that some processes are not well represented in the PMIP3 models. One challenge is to find adequate paleo observations against which to test these models. PMIP is now in phase 4 (part of CMIP6), which includes experiments covering five periods in Earth's history: the last millennium, last glacial maximum, last interglacial, and the mid-Pliocene. Newly compiled paleoclimate datasets from the PAGES2k project, more transient simulations, and participation of isotope enabled models planned for CMIP6PMIP4 will enable richer paleo data-model comparisons in the near future.

Kilbourne, Hali↗