Small RNAs bound to Argonaute proteins recognize partially or fully complementary nucleic acid targets in diverse gene-silencing processes. A subgroup of the Argonaute proteins--known as the 'Piwi family'--is required for germ- and stem-cell development in invertebrates, and two Piwi members--MILI and MIWI--are essential for spermatogenesis in mouse. Here we describe a new class of small RNAs that bind to MILI in mouse male germ cells, where they accumulate at the onset of meiosis. The sequences of the over 1,000 identified unique molecules share a strong preference for a 5' uridine, but otherwise cannot be readily classified into sequence families. Genomic mapping of these small RNAs reveals a limited number of clusters, suggesting that these RNAs are processed from long primary transcripts. The small RNAs are 26-31 nucleotides (nt) in length--clearly distinct from the 21-23 nt of microRNAs (miRNAs) or short interfering RNAs (siRNAs)--and we refer to them as 'Piwi-interacting RNAs' or piRNAs. Orthologous human chromosomal regions also give rise to small RNAs with the characteristics of piRNAs, but the cloned sequences are distinct. The identification of this new class of small RNAs provides an important starting point to determine the molecular function of Piwi proteins in mammalian spermatogenesis.

The establishment and maintenance of spermatogenesis in mammals requires specialized networks of gene expression programs in the testis. The gonad-specific TAF4b component of TFIID (formerly TAF II 105) is a transcriptional regulator enriched in the mouse testis. Herein we show that TAF4b is required for maintenance of spermatogenesis in the mouse. While young Taf4b-null males are initially fertile, Taf4b-null males become infertile by 3 mo of age and eventually exhibit seminiferous tubules devoid of germ cells. At birth, testes of Taf4b-null males appear histologically normal; however, at post-natal day 3 gonocyte proliferation is impaired and expression of spermatogonial stem cell markers c-Ret, Plzf, and Stra8 is reduced. Together, these data indicate that TAF4b is required for the precise expression of gene products essential for germ cell proliferation and suggest that TAF4b may be required for the regulation of spermatogonial stem cell specification and proliferation that is obligatory for normal spermatogenic maintenance in the adult. Spermatogenesis is a complex process requiring the specialized function of multiple cell types including somatic and germ cells that collectively results in the continuous production of functional sperm in adult males. The unlimited production of male gametes is largely accomplished through the ability of spermatogonial stem cells to self-renew in the adult testis. These complex and multifaceted events are dependent on appropriate expression and action of specific genes at multiple stages of germ cell and testicular development (Matzuk and Lamb 2002;McLaren 2003). The precise temporal and spatial expression of specific transcription factors is also essential for proper execution of spermatogenesis (SassoneCorsi 1997). Emerging evidence now suggests that in addition to gonad-specific transcription factors, specialized components of the basal RNA Polymerase II machinery are also critical for the execution of gonad-specific programs of gene expression (Hochheimer and Tjian 2003).The TFIID complex is a core RNA polymerase complex that contains the TATA-binding protein (TBP) and 14 TBP-associated factors (TAFs) that function in core promoter recognition and activator-dependent RNA Polymerase II recruitment (Verrijzer and Tjian 1996). While most TFIID subunits are expressed and function broadly in most cell types, there are selective TFIID subunits that apparently have evolved to function in the specification of gonadal-specific programs of gene expression. In the mouse, TAF4b is a component of TFIID that is highly enriched in gonadal tissues and is required for ovarian follicle development (Freiman et al. 2001). TAF4b is similar in structure to its broadly expressed paralog TAF4 (TAF II 130). While TAF4 and TAF4b display overlapping expression patterns in certain cell types, TAF4b is essential for regulating the selective expression of ovarian-specific gene expression patterns required for female fertility (Freiman et al. 2001).Several other members of the basal transcription mac...

Modern complex societies exhibit marked resilience to interannual-to- decadal droughts, but cultural responses to multidecadal-to-multicentury droughts can only be addressed by integrating detailed archaeological and paleoclimatic records. Four case studies drawn from New and Old World civilizations document societal responses to prolonged drought, including population dislocations, urban abandonment, and state collapse. Further study of past cultural adaptations to persistent climate change may provide valuable perspective on possible responses of modern societies to future climate change.