Pressing information - p345

doi:10.1038/nsmb0409-345

One aim in science communication is to make the general public more aware of the breakthroughs and insights basic science research provides. Our press office gives us one route to help achieve that goal.

Full Text - Pressing information | PDF (220 KB) - Pressing information

miR-9 and TLX: chasing tails in neural stem cells - pp346 - 347

Ahmet M Denli, Xinwei Cao & Fred H Gage

doi:10.1038/nsmb0409-346

Development and maintenance of an organism require the precise spatiotemporal orchestration of stem cell proliferation and differentiation. In neurogenesis, a microRNA and an orphan nuclear receptor comprise a negative feedback loop that regulates neural stem cell fate.

Full Text - miR-9 and TLX: chasing tails in neural stem cells | PDF (189 KB) - miR-9 and TLX: chasing tails in neural stem cells

See also: Article by Zhao et al.

A tipping point for mistranslation and disease - pp348 - 349

Paul Schimmel & Min Guo

doi:10.1038/nsmb0409-348

Two papers present strong evidence that the codon-anticodon interaction is poised on a tipping point so that, given a nudge, the tRNA can insert the wrong amino acid into the growing polypeptide chain, leading to translational fidelity loss.

Full Text - A tipping point for mistranslation and disease | PDF (710 KB) - A tipping point for mistranslation and disease

See also: Article by Murakami et al. | Article by Ledoux et al.

At the (3') end, you'll turn to meiosis - pp350 - 351

Alberto Moldón & José Ayté

doi:10.1038/nsmb0409-350

Many cellular fates are determined by different genetic programs, but the regulation of cellular differentiation is still not well understood. Besides the possible control exerted by the activity and combination of transcription factors, there are multiple RNA processing mechanisms, ensuring differential gene expression.

Full Text - At the (3') end, you'll turn to meiosis | PDF (186 KB) - At the (3') end, you'll turn to meiosis

Yeast as budding stem cells? - p351

Inês Chen

doi:10.1038/nsmb0409-351

Full Text - Yeast as budding stem cells? | PDF (147 KB) - Yeast as budding stem cells?

Research highlights - p352

doi:10.1038/nsmb0409-352

Full Text - Research highlights | PDF (138 KB) - Research highlights

Bases in the anticodon loop of tRNA^Ala_GGC prevent misreading - pp353 - 358

Hiroshi Murakami, Atsushi Ohta & Hiroaki Suga

doi:10.1038/nsmb.1580

The conserved A32-U38 pair in the anticodon loop of tRNA^Ala_GGC is now shown to be important for accurate decoding. Using tRNA^Ala variants in this pair in an in vitro translation system showed that some variants could decode both the cognate and a near-cognate codons with high efficiency. These mutants tRNA were toxic in vivo, supporting the biological relevance of this accuracy determinant.

Abstract - | Full Text - Bases in the anticodon loop of tRNAAlaGGC prevent misreading | PDF (600 KB) - Bases in the anticodon loop of tRNAAlaGGC prevent misreading | Supplementary information

See also: News and Views by Schimmel & Guo

A sequence element that tunes Escherichia coli tRNA^Ala_GGC to ensure accurate decoding - pp359 - 364

Sarah Ledoux, Mikoaj Olejniczak & Olke C Uhlenbeck

doi:10.1038/nsmb.1581

The conserved A32-U38 pair in the anticodon loop of tRNA^Ala_GGC is now shown to be important for accurate decoding. Pre–steady state kinetic analyses of mutants in A32-U38 show that they can efficiently decode near-cognate codons, with a mismatch in any of the three positions, pointing to the role of such conserved sequence elements in suppressing misreading during translation.

Abstract - | Full Text - A sequence element that tunes Escherichia coli tRNAAlaGGC to ensure accurate decoding | PDF (498 KB) - A sequence element that tunes Escherichia coli tRNAAlaGGC to ensure accurate decoding | Supplementary information

See also: News and Views by Schimmel & Guo

A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination - pp365 - 371

Chunnian Zhao, GuoQiang Sun, Shengxiu Li & Yanhong Shi

doi:10.1038/nsmb.1576

MicroRNAs are involved in post-transcriptional regulation of gene expression. Data now indicate that miR-9 targets the nuclear receptor TLX and vice versa, thus proposing a regulatory circuit linked to the switch between neural progenitor proliferation and differentiation.

Abstract - | Full Text - A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination | PDF (831 KB) - A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination | Supplementary information

See also: News and Views by Denli et al.

TRF2 functions as a protein hub and regulates telomere maintenance by recognizing specific peptide motifs - pp372 - 379

Hyeung Kim, Ok-Hee Lee, Huawei Xin, Liuh-Yow Chen, Jun Qin, Heekyung Kate Chae, Shiaw-Yih Lin, Amin Safari, Dan Liu & Zhou Songyang

doi:10.1038/nsmb.1575

TRF2 is a member of the telosome/shelterin complex, which helps maintain telomere integrity. Using an oriented peptide library based on a previously identified TRF2-interaction region to define a consensus sequence for binding, new proteins have been identified as TRF2 interactors and implicated in telomeric functions. This suggests that TRF2 acts as a hub for recruiting different proteins to the telomere via a distinct linear sequence.

Abstract - | Full Text - TRF2 functions as a protein hub and regulates telomere maintenance by recognizing specific peptide motifs | PDF (721 KB) - TRF2 functions as a protein hub and regulates telomere maintenance by recognizing specific peptide motifs | Supplementary information

Polyglutamine disruption of the huntingtin exon 1 N terminus triggers a complex aggregation mechanism - pp380 - 389

Ashwani K Thakur, Murali Jayaraman, Rakesh Mishra, Monika Thakur, Veronique M Chellgren, In-Ja L Byeon, Dalaver H Anjum, Ravindra Kodali, Trevor P Creamer, James F Conway, Angela M Gronenborn & Ronald Wetzel

doi:10.1038/nsmb.1570

The huntingtin protein (HTT) contains a polyQ tract preceded by an N-terminal flanking sequence (HTT^NT) that contributes to HTT aggregation. Now the role of HTT^NT in aggregation is explored in vitro, revealing a complex, multistep pathway initiated when polyQ disrupts HTT^NT structure, enhancing the latter's assembly into prefibrillar aggregates. Within these intermediates, subsequent interactions of the polyQ moieties drive further assembly into compact amyloid aggregates.

Abstract - | Full Text - Polyglutamine disruption of the huntingtin exon 1 N terminus triggers a complex aggregation mechanism | PDF (1,116 KB) - Polyglutamine disruption of the huntingtin exon 1 N terminus triggers a complex aggregation mechanism

Bacterial frataxin CyaY is the gatekeeper of iron-sulfur cluster formation catalyzed by IscS - pp390 - 396

Salvatore Adinolfi, Clara Iannuzzi, Filippo Prischi, Chiara Pastore, Stefania Iametti, Stephen R Martin, Franco Bonomi & Annalisa Pastore

doi:10.1038/nsmb.1579

Frataxin is a conserved protein involved in the cellular assembly of iron-sulfur clusters, but its exact role is not clear. Now work on bacterial frataxin CyaY indicates that it acts as an iron-dependent regulator of iron-sulfur cluster formation by the desulfurase IscS.

Abstract - | Full Text - Bacterial frataxin CyaY is the gatekeeper of iron-sulfur cluster formation catalyzed by IscS | PDF (677 KB) - Bacterial frataxin CyaY is the gatekeeper of iron-sulfur cluster formation catalyzed by IscS | Supplementary information

The pathway of hepatitis C virus mRNA recruitment to the human ribosome - pp397 - 404

Christopher S Fraser, John W B Hershey & Jennifer A Doudna

doi:10.1038/nsmb.1572

Some viruses, including hepatitis C virus (HCV), bypass cellular initiation factors and can initiate translation through an internal ribosomal entry site (IRES). This process is now examined for the HCV IRES, indicating that conformational changes are necessary but not sufficient for initiation. Instead, the initiator tRNA, but not its interaction with the start codon, seems key to stabilizing HCV mRNA binding to the ribosome, indicating that this IRES bypasses some, but not all, of the functions of the initiation factors.

Abstract - | Full Text - The pathway of hepatitis C virus mRNA recruitment to the human ribosome | PDF (836 KB) - The pathway of hepatitis C virus mRNA recruitment to the human ribosome | Supplementary information

Tertiary interactions within the ribosomal exit tunnel - pp405 - 411

Andrey Kosolapov & Carol Deutsch

doi:10.1038/nsmb.1571

Although the dimensions of the ribosomal exit tunnel are cramped, it is known that some structural elements can begin folding there. The tertiary folding of an -helical hairpin and a -hairpin are now probed within the ribosomal exit tunnel, indicating that minimal tertiary interactions can be explored close to the exit of the tunnel.

Abstract - | Full Text - Tertiary interactions within the ribosomal exit tunnel | PDF (531 KB) - Tertiary interactions within the ribosomal exit tunnel | Supplementary information

Acetylation by GCN5 regulates CDC6 phosphorylation in the S phase of the cell cycle - pp412 - 420

Roberta Paolinelli, Ramiro Mendoza-Maldonado, Anna Cereseto & Mauro Giacca

doi:10.1038/nsmb.1583

CDC6 is involved in the assembly of pre-replicative complexes. CDC6 is now found to be acetylated by GCN5, a modification that leads to subsequent phosphorylation at sites targeted by by Cyclin A during S phase, thus regulating stability and subcellular localization.

Abstract - | Full Text - Acetylation by GCN5 regulates CDC6 phosphorylation in the S phase of the cell cycle | PDF (854 KB) - Acetylation by GCN5 regulates CDC6 phosphorylation in the S phase of the cell cycle | Supplementary information

Regulation of active site coupling in glutamine-dependent NAD⁺ synthetase - pp421 - 429

Nicole LaRonde-LeBlanc, Melissa Resto & Barbara Gerratana

doi:10.1038/nsmb.1567

• PDB code

  • 3DLA

• 3D view

  • 3DLA

NAD⁺ is an essential cofactor in energy metabolism and redox reactions and is a regulator of different cellular processes. Kinetic and structural studies of the
M. tuberculosis glutamine-dependent NAD⁺ synthetase suggests a tight coupling of the catalytic sites that catalyzes the ATP-dependent formation of NAD⁺ at the synthetase domain using the ammonia derived from the L-glutamine and glutaminase domain.

Abstract - | Full Text - Regulation of active site coupling in glutamine-dependent NAD+ synthetase | PDF (1,156 KB) - Regulation of active site coupling in glutamine-dependent NAD+ synthetase | Supplementary information

Precursor-product discrimination by La protein during tRNA metabolism - pp430 - 437

Mark A Bayfield & Richard J Maraia

doi:10.1038/nsmb.1573

The La protein binds precursor tRNAs at their 3' ends, thus facilitating maturation. Crystal structures indicate that the most obvious RNA-recognition motif does not bind this pre-tRNA tail, but studies now indicate that La has two distinct binding sites for the pre-mRNA. Recognition through these two sites may help distinguish precursor from product, an idea supported by biochemical studies here.

Abstract - | Full Text - Precursor-product discrimination by La protein during tRNA metabolism | PDF (656 KB) - Precursor-product discrimination by La protein during tRNA metabolism | Supplementary information

S16 throws a conformational switch during assembly of 30S 5' domain - pp438 - 445

Priya Ramaswamy & Sarah A Woodson

doi:10.1038/nsmb.1585

Ribosomal proteins are known to play an important role in determining rRNA structure. The body of the 30S ribosomal subunit is formed by the 16S rRNA 5' domain. New data indicate that the assembly protein S16 discriminates between folding intermediates of the 5' domain, increasing cooperative 30S assembly and stabilizing interactions at its decoding site.

Abstract - | Full Text - S16 throws a conformational switch during assembly of 30S 5' domain | PDF (1,111 KB) - S16 throws a conformational switch during assembly of 30S 5' domain | Supplementary information

CK2 phosphorylates BMAL1 to regulate the mammalian clock - pp446 - 448

Teruya Tamaru, Jun Hirayama, Yasushi Isojima, Katsuya Nagai, Shigemi Norioka, Ken Takamatsu & Paolo Sassone-Corsi

doi:10.1038/nsmb.1578

BMAL1 has a central role in the mammalian circadian clock, acting as a transcriptional activator. The activity of BMAL1 is controlled by post-translational modifications such as acetylation and SUMOylation. Now the kinase CK2a is shown to phosphorylate BMAL1 at Ser90, and this is essential for BMAL1's function in the circadian clock.

Abstract - | Full Text - CK2 phosphorylates BMAL1 to regulate the mammalian clock | PDF (407 KB) - CK2 phosphorylates BMAL1 to regulate the mammalian clock | Supplementary information

Distinct transcriptional outputs associated with mono- and dimethylated histone H3 arginine 2 - pp449 - 451

Antonis Kirmizis, Helena Santos-Rosa, Christopher J Penkett, Michael A Singer, Roland D Green & Tony Kouzarides

doi:10.1038/nsmb.1569

Methylation at particular residues on histone tails has been associated with various functions and, in the case of dimethylated histone H3 arginine 2 (H3R2), cross-talk with methylation of a nearby lysine has been shown to be linked to transcriptional repression. Budding yeast monomethylated H3R2 is now shown to be associated with active loci and involved in activation of meiotic genes upon induction of sporulation.

Abstract - | Full Text - Distinct transcriptional outputs associated with mono- and dimethylated histone H3 arginine 2 | PDF (332 KB) - Distinct transcriptional outputs associated with mono- and dimethylated histone H3 arginine 2 | Supplementary information